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data-trace="false" data-dom-id="Pill-react-component-ddaf8317-26b9-49c6-a405-37641ad65e68"></div> <div id="Pill-react-component-ddaf8317-26b9-49c6-a405-37641ad65e68"></div> </a></div></div></div></div><div class="right-panel-container"><div class="user-content-wrapper"><div class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Arun K Haldar</h3></div><div class="js-work-strip profile--work_container" data-work-id="74428355"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/74428355/Guanylate_Binding_Proteins_Restrict_Leishmania_donovani_Growth_in_Nonphagocytic_Cells_Independent_of_Parasitophorous_Vacuolar_Targeting"><img alt="Research paper thumbnail of Guanylate Binding Proteins Restrict Leishmania donovani Growth in Nonphagocytic Cells Independent of Parasitophorous Vacuolar Targeting" class="work-thumbnail" src="https://attachments.academia-assets.com/82585654/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/74428355/Guanylate_Binding_Proteins_Restrict_Leishmania_donovani_Growth_in_Nonphagocytic_Cells_Independent_of_Parasitophorous_Vacuolar_Targeting">Guanylate Binding Proteins Restrict Leishmania donovani Growth in Nonphagocytic Cells Independent of Parasitophorous Vacuolar Targeting</a></div><div class="wp-workCard_item"><span>mBio</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Interferon (IFN)-inducible guanylate binding proteins (GBPs) play important roles in host defense...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Interferon (IFN)-inducible guanylate binding proteins (GBPs) play important roles in host defense against many intracellular pathogens that reside within pathogen-containing vacuoles (PVs). For instance, members of the GBP family translocate to PVs occupied by the protozoan pathogen Toxoplasma and facilitate PV disruption and lytic parasite killing. While the GBP defense program targeting Toxoplasma has been studied in some detail, the role of GBPs in host defense to other protozoan pathogens is poorly characterized. Here, we report a critical role for both mouse and human GBPs in the cell-autonomous immune response against the vector-borne parasite Leishmania donovani. Although L. donovani can infect both phagocytic and nonphagocytic cells, it predominantly replicates inside professional phagocytes. The underlying basis for this cell type tropism is unclear. Here, we demonstrate that GBPs restrict growth of L. donovani in both mouse and human nonphagocytic cells. GBP-mediated restr...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="76ece5a756f7703da230aa9c87061b6a" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":82585654,"asset_id":74428355,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/82585654/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="74428355"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="74428355"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 74428355; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=74428355]").text(description); $(".js-view-count[data-work-id=74428355]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 74428355; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='74428355']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "76ece5a756f7703da230aa9c87061b6a" } } $('.js-work-strip[data-work-id=74428355]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":74428355,"title":"Guanylate Binding Proteins Restrict Leishmania donovani Growth in Nonphagocytic Cells Independent of Parasitophorous Vacuolar Targeting","translated_title":"","metadata":{"abstract":"Interferon (IFN)-inducible guanylate binding proteins (GBPs) play important roles in host defense against many intracellular pathogens that reside within pathogen-containing vacuoles (PVs). For instance, members of the GBP family translocate to PVs occupied by the protozoan pathogen Toxoplasma and facilitate PV disruption and lytic parasite killing. While the GBP defense program targeting Toxoplasma has been studied in some detail, the role of GBPs in host defense to other protozoan pathogens is poorly characterized. Here, we report a critical role for both mouse and human GBPs in the cell-autonomous immune response against the vector-borne parasite Leishmania donovani. Although L. donovani can infect both phagocytic and nonphagocytic cells, it predominantly replicates inside professional phagocytes. The underlying basis for this cell type tropism is unclear. Here, we demonstrate that GBPs restrict growth of L. donovani in both mouse and human nonphagocytic cells. GBP-mediated restr...","publisher":"American Society for Microbiology","publication_name":"mBio"},"translated_abstract":"Interferon (IFN)-inducible guanylate binding proteins (GBPs) play important roles in host defense against many intracellular pathogens that reside within pathogen-containing vacuoles (PVs). For instance, members of the GBP family translocate to PVs occupied by the protozoan pathogen Toxoplasma and facilitate PV disruption and lytic parasite killing. While the GBP defense program targeting Toxoplasma has been studied in some detail, the role of GBPs in host defense to other protozoan pathogens is poorly characterized. Here, we report a critical role for both mouse and human GBPs in the cell-autonomous immune response against the vector-borne parasite Leishmania donovani. Although L. donovani can infect both phagocytic and nonphagocytic cells, it predominantly replicates inside professional phagocytes. The underlying basis for this cell type tropism is unclear. Here, we demonstrate that GBPs restrict growth of L. donovani in both mouse and human nonphagocytic cells. 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LPS-induced inflammation and resulting life-threatening sepsis are mediated by the two distinct LPS receptors TLR4 and caspase-4. Whereas the regulation of TLR4 activation by extracellular and phago-endosomal LPS has been studied in great detail, auxiliary host factors that specifically modulate recognition of cytosolic LPS by caspase-4 are largely unknown. This study identifies dynamin-related membrane remodeling proteins belonging to the family of Immunity related GTPases M clade (IRGM) as negative regulators of caspase-4 activation in macrophages. Phagocytes lacking expression of mouse isoform Irgm2 aberrantly activate caspase-4-dependent inflammatory responses when exposed to extracellular LPS, bacterial outer membrane vesicles or gram-negative bacteria. Consequently, Irgm2-deficient mice display increased susceptibility to caspase-4mediated septic shock in vivo. This Irgm2 phenotype is partly reversed by the simultaneous genetic deletion of the two additional Irgm paralogs Irgm1 and Irgm3, indicating that dysregulated Irgm isoform expression disrupts intracellular LPS processing pathways that limit LPS availability for caspase-4 activation.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b94ee82ff040ae778c16d4dc7f61cdc1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75776656,"asset_id":63301730,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75776656/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63301730"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63301730"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63301730; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=63301730]").text(description); $(".js-view-count[data-work-id=63301730]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 63301730; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='63301730']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b94ee82ff040ae778c16d4dc7f61cdc1" } } $('.js-work-strip[data-work-id=63301730]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":63301730,"title":"Dynamin-related Irgm proteins modulate LPS-induced caspase-4 activation and septic shock","translated_title":"","metadata":{"publisher":"Cold Spring Harbor Laboratory","grobid_abstract":"Inflammation associated with gram-negative bacterial infections is often instigated by the bacterial cell wall component lipopolysaccharide (LPS). 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Host guanylate binding proteins (GBPs) promote infection-induced caspase-11 activation in tissue culture models, and yet their in vivo role in LPS-mediated sepsis has remained unexplored. LPS can be released from lysed bacteria as &quot;free&quot; LPS aggregates or actively secreted by live bacteria as a component of outer membrane vesicles (OMVs). Here, we report that GBPs control inflammation and sepsis in mice injected with either free LPS or purified OMVs derived from Gram-negative Escherichia coli In agreement with our observations from in vivo experiments, we demonstrate that macrophages lacking GBP2 expression fail to induce pyroptotic cell death and proinflammatory interleukin-1β (IL-1β) and IL-18 secretion when exposed to OMVs. We ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="7dfffe0d438528a1d6b2111194085e94" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195658,"asset_id":59101353,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195658/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101353"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101353"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101353; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101353]").text(description); $(".js-view-count[data-work-id=59101353]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101353; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101353']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "7dfffe0d438528a1d6b2111194085e94" } } $('.js-work-strip[data-work-id=59101353]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101353,"title":"Inflammasome Activation by Bacterial Outer Membrane Vesicles Requires Guanylate Binding Proteins","translated_title":"","metadata":{"abstract":"The Gram-negative bacterial cell wall component lipopolysaccharide (LPS) is recognized by the noncanonical inflammasome protein caspase-11 in the cytosol of infected host cells and thereby prompts an inflammatory immune response linked to sepsis. 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It highlights how IFNg activates host cell mechanisms that lead to the attachment of polyubiquitin chains to these vacuoles, marking them for destruction. The research indicates that while murine cells utilize Immunity Related GTPases (IRGs) for this process, the mechanisms in human cells remain less understood and likely differ from the murine pathway. Ubiquitination appears essential for cell-autonomous immunity to these pathogens and involves multiple E3 ligases, suggesting a complex interaction in evoking immune responses.","publication_date":{"day":null,"month":null,"year":2015,"errors":{}},"publication_name":"Communicative \u0026 Integrative Biology"},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101350/Ubiquitination_of_pathogen_containing_vacuoles_promotes_host_defense_toChlamydia_trachomatisandToxoplasma_gondii","translated_internal_url":"","created_at":"2021-10-20T04:19:29.489-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195675,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195675/thumbnails/1.jpg","file_name":"pmc4802790.pdf","download_url":"https://www.academia.edu/attachments/73195675/download_file","bulk_download_file_name":"Ubiquitination_of_pathogen_containing_va.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195675/pmc4802790-libre.pdf?1634732266=\u0026response-content-disposition=attachment%3B+filename%3DUbiquitination_of_pathogen_containing_va.pdf\u0026Expires=1743659392\u0026Signature=R7Ns75Nqr0GRl~AxqyMui97dQWN5izMFWn5-kXhGWbFrjRdUc7LOJ7SPtITVoQ0vj6yQaBOPmauEUnaQAav38j2MifS~cVRzcPFNccMwDgDdPO66t0v8fhMNUsfkb6W4HPaAfXNw5zhE83IQSRoQ7VgtGVxHyZks0J7YQ-kpSeuIYckCr2M8Vlxk-bmMnsUB5t5fLT-~bssDzu0ZEqEmCtyBphPqAoxM21YIBClTUIHJ-339bik07dyAMuKpf-vWD3OeRpi2Z99tObi7k3VTHw4D3pLefCJVC~xshwicamFDRdQeKbqV-YuNOg~CQ6d6TwqW3uf4jL6JzcWom3n-Tw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Ubiquitination_of_pathogen_containing_vacuoles_promotes_host_defense_toChlamydia_trachomatisandToxoplasma_gondii","translated_slug":"","page_count":3,"language":"en","content_type":"Work","summary":null,"owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195675,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195675/thumbnails/1.jpg","file_name":"pmc4802790.pdf","download_url":"https://www.academia.edu/attachments/73195675/download_file","bulk_download_file_name":"Ubiquitination_of_pathogen_containing_va.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195675/pmc4802790-libre.pdf?1634732266=\u0026response-content-disposition=attachment%3B+filename%3DUbiquitination_of_pathogen_containing_va.pdf\u0026Expires=1743659392\u0026Signature=R7Ns75Nqr0GRl~AxqyMui97dQWN5izMFWn5-kXhGWbFrjRdUc7LOJ7SPtITVoQ0vj6yQaBOPmauEUnaQAav38j2MifS~cVRzcPFNccMwDgDdPO66t0v8fhMNUsfkb6W4HPaAfXNw5zhE83IQSRoQ7VgtGVxHyZks0J7YQ-kpSeuIYckCr2M8Vlxk-bmMnsUB5t5fLT-~bssDzu0ZEqEmCtyBphPqAoxM21YIBClTUIHJ-339bik07dyAMuKpf-vWD3OeRpi2Z99tObi7k3VTHw4D3pLefCJVC~xshwicamFDRdQeKbqV-YuNOg~CQ6d6TwqW3uf4jL6JzcWom3n-Tw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101350-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101346"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101346/Ubiquitin_systems_mark_pathogen_containing_vacuoles_as_targets_for_host_defense_by_guanylate_binding_proteins"><img alt="Research paper thumbnail of Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/73195672/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101346/Ubiquitin_systems_mark_pathogen_containing_vacuoles_as_targets_for_host_defense_by_guanylate_binding_proteins">Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins</a></div><div class="wp-workCard_item"><span>Proceedings of the National Academy of Sciences</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche pe...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f2eb507af94090838c9674d63848711c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195672,"asset_id":59101346,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195672/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101346"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101346"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101346; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101346]").text(description); $(".js-view-count[data-work-id=59101346]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101346; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101346']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "f2eb507af94090838c9674d63848711c" } } $('.js-work-strip[data-work-id=59101346]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101346,"title":"Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins","translated_title":"","metadata":{"abstract":"Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage ...","publisher":"Proceedings of the National Academy of Sciences","ai_title_tag":"Ubiquitin marks pathogen vacuoles for GBP-mediated immunity","publication_date":{"day":null,"month":null,"year":2015,"errors":{}},"publication_name":"Proceedings of the National Academy of Sciences"},"translated_abstract":"Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage ...","internal_url":"https://www.academia.edu/59101346/Ubiquitin_systems_mark_pathogen_containing_vacuoles_as_targets_for_host_defense_by_guanylate_binding_proteins","translated_internal_url":"","created_at":"2021-10-20T04:19:29.305-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195672,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195672/thumbnails/1.jpg","file_name":"E5628.full.pdf","download_url":"https://www.academia.edu/attachments/73195672/download_file","bulk_download_file_name":"Ubiquitin_systems_mark_pathogen_containi.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195672/E5628.full-libre.pdf?1634732270=\u0026response-content-disposition=attachment%3B+filename%3DUbiquitin_systems_mark_pathogen_containi.pdf\u0026Expires=1743659392\u0026Signature=EUQ3ySBQDyqhgq0AB3M5F-Impv76IjAbloi3F17LKq71NuDzEVIkYgw8ZOm7feMzlzdku31gXt~AnoxJty6y3yE1i0ljTa9uAQ9AYV04yYkYFqtQXXEEjylU-2Oh8VY0ckzU-jJWItNn6yN9qOCJCIlYbMI-7BHQgYQek6b0wWYezTie5RbiLH~idYpuZ73X~RFM44TJ3hUygQM9grGy-quVhiNjzNTAEVIkiIw2EP8vsaSI2NPoND4UYZ-zwaTeA21iMBn8DUArTe8OXzddfa5ZA~9jOKkFy-uJDpWUiobRgoXWX~dBjD~FfA9kQ5qAQ-HeKyyoonVyfUkr2d0slA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Ubiquitin_systems_mark_pathogen_containing_vacuoles_as_targets_for_host_defense_by_guanylate_binding_proteins","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage ...","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195672,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195672/thumbnails/1.jpg","file_name":"E5628.full.pdf","download_url":"https://www.academia.edu/attachments/73195672/download_file","bulk_download_file_name":"Ubiquitin_systems_mark_pathogen_containi.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195672/E5628.full-libre.pdf?1634732270=\u0026response-content-disposition=attachment%3B+filename%3DUbiquitin_systems_mark_pathogen_containi.pdf\u0026Expires=1743659392\u0026Signature=EUQ3ySBQDyqhgq0AB3M5F-Impv76IjAbloi3F17LKq71NuDzEVIkYgw8ZOm7feMzlzdku31gXt~AnoxJty6y3yE1i0ljTa9uAQ9AYV04yYkYFqtQXXEEjylU-2Oh8VY0ckzU-jJWItNn6yN9qOCJCIlYbMI-7BHQgYQek6b0wWYezTie5RbiLH~idYpuZ73X~RFM44TJ3hUygQM9grGy-quVhiNjzNTAEVIkiIw2EP8vsaSI2NPoND4UYZ-zwaTeA21iMBn8DUArTe8OXzddfa5ZA~9jOKkFy-uJDpWUiobRgoXWX~dBjD~FfA9kQ5qAQ-HeKyyoonVyfUkr2d0slA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":13346,"name":"Toxoplasma","url":"https://www.academia.edu/Documents/in/Toxoplasma"},{"id":24706,"name":"Innate immunity","url":"https://www.academia.edu/Documents/in/Innate_immunity"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":34106,"name":"Chlamydia trachomatis","url":"https://www.academia.edu/Documents/in/Chlamydia_trachomatis"},{"id":37798,"name":"Toxoplasmosis","url":"https://www.academia.edu/Documents/in/Toxoplasmosis"},{"id":55266,"name":"Ubiquitin","url":"https://www.academia.edu/Documents/in/Ubiquitin"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":143257,"name":"PNAS","url":"https://www.academia.edu/Documents/in/PNAS"},{"id":279576,"name":"Immune Evasion","url":"https://www.academia.edu/Documents/in/Immune_Evasion"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":2428330,"name":"Vacuoles","url":"https://www.academia.edu/Documents/in/Vacuoles"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101346-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101343"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101343/Guanylate_Binding_Proteins_enable_rapid_activation_of_canonical_and_noncanonical_inflammasomes_in_Chlamydia_infected_macrophages"><img alt="Research paper thumbnail of Guanylate Binding Proteins enable rapid activation of canonical and noncanonical inflammasomes in Chlamydia-infected macrophages" class="work-thumbnail" src="https://attachments.academia-assets.com/73195665/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101343/Guanylate_Binding_Proteins_enable_rapid_activation_of_canonical_and_noncanonical_inflammasomes_in_Chlamydia_infected_macrophages">Guanylate Binding Proteins enable rapid activation of canonical and noncanonical inflammasomes in Chlamydia-infected macrophages</a></div><div class="wp-workCard_item"><span>Infection and immunity</span><span>, Jan 28, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Interferon (IFN)-inducible Guanylate Binding Proteins (GBPs) mediate cell-autonomous host resista...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Interferon (IFN)-inducible Guanylate Binding Proteins (GBPs) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. The prevailing model postulates that these two GBP-controlled activities are directly linked through GBP-dependent vacuolar lysis. It was proposed that rupture of pathogen-containing vacuoles (PVs) by GBPs destroyed the microbial refuge and simultaneously contaminated the host cell cytosol with microbial activators of inflammasomes. Here, we demonstrate that GBP-mediated host resistance and GBP-mediated inflammatory responses can be uncoupled. We show that PVs formed by the rodent pathogen Chlamydia muridarum, so-called inclusions, remain free of GBPs and that C. muridarum is impervious to GBP-mediated restrictions on bacterial growth. Although GBPs neither bind to C. muridarum inclusions nor restrict C. muridarum growth, we find that GBPs promote inflammasome activation in C. muridarum-infected macrophages. We demonstrate t...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="74dfffa3e02436a8ff8d919521d3c70c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195665,"asset_id":59101343,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195665/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101343"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101343"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101343; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101343]").text(description); $(".js-view-count[data-work-id=59101343]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101343; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101343']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "74dfffa3e02436a8ff8d919521d3c70c" } } $('.js-work-strip[data-work-id=59101343]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101343,"title":"Guanylate Binding Proteins enable rapid activation of canonical and noncanonical inflammasomes in Chlamydia-infected macrophages","translated_title":"","metadata":{"abstract":"Interferon (IFN)-inducible Guanylate Binding Proteins (GBPs) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. The prevailing model postulates that these two GBP-controlled activities are directly linked through GBP-dependent vacuolar lysis. It was proposed that rupture of pathogen-containing vacuoles (PVs) by GBPs destroyed the microbial refuge and simultaneously contaminated the host cell cytosol with microbial activators of inflammasomes. Here, we demonstrate that GBP-mediated host resistance and GBP-mediated inflammatory responses can be uncoupled. We show that PVs formed by the rodent pathogen Chlamydia muridarum, so-called inclusions, remain free of GBPs and that C. muridarum is impervious to GBP-mediated restrictions on bacterial growth. Although GBPs neither bind to C. muridarum inclusions nor restrict C. muridarum growth, we find that GBPs promote inflammasome activation in C. muridarum-infected macrophages. We demonstrate t...","publication_date":{"day":28,"month":1,"year":2015,"errors":{}},"publication_name":"Infection and immunity"},"translated_abstract":"Interferon (IFN)-inducible Guanylate Binding Proteins (GBPs) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. The prevailing model postulates that these two GBP-controlled activities are directly linked through GBP-dependent vacuolar lysis. It was proposed that rupture of pathogen-containing vacuoles (PVs) by GBPs destroyed the microbial refuge and simultaneously contaminated the host cell cytosol with microbial activators of inflammasomes. Here, we demonstrate that GBP-mediated host resistance and GBP-mediated inflammatory responses can be uncoupled. We show that PVs formed by the rodent pathogen Chlamydia muridarum, so-called inclusions, remain free of GBPs and that C. muridarum is impervious to GBP-mediated restrictions on bacterial growth. Although GBPs neither bind to C. muridarum inclusions nor restrict C. muridarum growth, we find that GBPs promote inflammasome activation in C. muridarum-infected macrophages. 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We demonstrate t...","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195665,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195665/thumbnails/1.jpg","file_name":"4740.full.pdf","download_url":"https://www.academia.edu/attachments/73195665/download_file","bulk_download_file_name":"Guanylate_Binding_Proteins_enable_rapid.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195665/4740.full-libre.pdf?1634732272=\u0026response-content-disposition=attachment%3B+filename%3DGuanylate_Binding_Proteins_enable_rapid.pdf\u0026Expires=1743659393\u0026Signature=fGc6BHytyUNPsXf2KftVs-neHfjNDjy-9-Vej~1PAH--WXLamI6nKukCTC1USXJ5WhydxhIHMUlNvpRZs--99KNo8uFKqx8fIi3EDfecs3OFWh~9QWnpvcJ-ABuriL001ArUyoaphbK5eqA2YOI5-Zj5sTbsjBqN~45QQIkUui~QLh8taqmCabEdAVCNBCLj3iZ1XaUNvtWdIXLPSgNk3-~1Xgoz-N6kZl50j7M-vx5ioTeAXpXB~ZEK9jUmHIxpJJhglA6P3rVW4ubDfb~UHPqeq6~NVFWrLK-tjqIDoCbPpqxjwaMIXtVMLx7hVVun3CCDOsZJGrWNKKLu~T6mEg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":34106,"name":"Chlamydia trachomatis","url":"https://www.academia.edu/Documents/in/Chlamydia_trachomatis"},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":48758,"name":"Infection and immunity","url":"https://www.academia.edu/Documents/in/Infection_and_immunity"},{"id":50841,"name":"Caspases","url":"https://www.academia.edu/Documents/in/Caspases"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":284067,"name":"Inclusion Bodies","url":"https://www.academia.edu/Documents/in/Inclusion_Bodies"},{"id":585385,"name":"Primary Cell Culture","url":"https://www.academia.edu/Documents/in/Primary_Cell_Culture"},{"id":743643,"name":"Host Pathogen Interactions","url":"https://www.academia.edu/Documents/in/Host_Pathogen_Interactions"},{"id":886608,"name":"Inflammasomes","url":"https://www.academia.edu/Documents/in/Inflammasomes"},{"id":1186610,"name":"DNA binding proteins","url":"https://www.academia.edu/Documents/in/DNA_binding_proteins"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":1763968,"name":"Gene Expression Regulation","url":"https://www.academia.edu/Documents/in/Gene_Expression_Regulation"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":2428330,"name":"Vacuoles","url":"https://www.academia.edu/Documents/in/Vacuoles"},{"id":2533047,"name":"fibroblasts","url":"https://www.academia.edu/Documents/in/fibroblasts"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101343-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101341"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101341/Use_of_Antimony_in_the_Treatment_of_Leishmaniasis_Current_Status_and_Future_Directions"><img alt="Research paper thumbnail of Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions" class="work-thumbnail" src="https://attachments.academia-assets.com/73195663/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101341/Use_of_Antimony_in_the_Treatment_of_Leishmaniasis_Current_Status_and_Future_Directions">Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions</a></div><div class="wp-workCard_item"><span>Molecular Biology International</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonial...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V)in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistantLeishmania donovaniisolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b92901833db3351d6c3e52ab77f61739" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195663,"asset_id":59101341,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195663/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101341"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101341"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101341; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101341]").text(description); $(".js-view-count[data-work-id=59101341]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101341; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101341']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b92901833db3351d6c3e52ab77f61739" } } $('.js-work-strip[data-work-id=59101341]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101341,"title":"Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions","translated_title":"","metadata":{"abstract":"In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V)in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistantLeishmania donovaniisolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.","publisher":"Hindawi Limited","ai_title_tag":"Antimony Treatment in Leishmaniasis: Mechanisms and Advances","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Molecular Biology International"},"translated_abstract":"In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V)in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistantLeishmania donovaniisolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.","internal_url":"https://www.academia.edu/59101341/Use_of_Antimony_in_the_Treatment_of_Leishmaniasis_Current_Status_and_Future_Directions","translated_internal_url":"","created_at":"2021-10-20T04:19:29.114-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195663,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195663/thumbnails/1.jpg","file_name":"56c5214eaa5ae3d8169e680f97b6c566e8e0.pdf","download_url":"https://www.academia.edu/attachments/73195663/download_file","bulk_download_file_name":"Use_of_Antimony_in_the_Treatment_of_Leis.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195663/56c5214eaa5ae3d8169e680f97b6c566e8e0-libre.pdf?1634732273=\u0026response-content-disposition=attachment%3B+filename%3DUse_of_Antimony_in_the_Treatment_of_Leis.pdf\u0026Expires=1743659393\u0026Signature=PaKSIiJvyblWV7C35fp-2CK2Ff~RK5M2Ttqgd-pvxKL8ileo95BFu6T4JYlA399d3836Ry3QdNhpdvjridCjuQJJWilhTa37Jgpejuq31nBldqvd9oE0-gTxVM8XIjwCcTbwm0PqkF-vxlSw~x~2EIpZuP3awfORUJyfXK7uysBaO8S69Co0eqtrAe0PPG9FDjWH~k8kL9SUlFvFhRO9rr4VTlVzrpVJ83xJkepp40E38ZD-D-2p~l2Wnty~UkBDNldJAazXMcgkXp3JMtQ6kI9MlFUxmCyYvd9w-O7bNoOaUSc-87l42zLGDAZcee5ADUNmJpQHNjO51l56KEJhiQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Use_of_Antimony_in_the_Treatment_of_Leishmaniasis_Current_Status_and_Future_Directions","translated_slug":"","page_count":23,"language":"en","content_type":"Work","summary":"In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V)in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistantLeishmania donovaniisolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195663,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195663/thumbnails/1.jpg","file_name":"56c5214eaa5ae3d8169e680f97b6c566e8e0.pdf","download_url":"https://www.academia.edu/attachments/73195663/download_file","bulk_download_file_name":"Use_of_Antimony_in_the_Treatment_of_Leis.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195663/56c5214eaa5ae3d8169e680f97b6c566e8e0-libre.pdf?1634732273=\u0026response-content-disposition=attachment%3B+filename%3DUse_of_Antimony_in_the_Treatment_of_Leis.pdf\u0026Expires=1743659393\u0026Signature=PaKSIiJvyblWV7C35fp-2CK2Ff~RK5M2Ttqgd-pvxKL8ileo95BFu6T4JYlA399d3836Ry3QdNhpdvjridCjuQJJWilhTa37Jgpejuq31nBldqvd9oE0-gTxVM8XIjwCcTbwm0PqkF-vxlSw~x~2EIpZuP3awfORUJyfXK7uysBaO8S69Co0eqtrAe0PPG9FDjWH~k8kL9SUlFvFhRO9rr4VTlVzrpVJ83xJkepp40E38ZD-D-2p~l2Wnty~UkBDNldJAazXMcgkXp3JMtQ6kI9MlFUxmCyYvd9w-O7bNoOaUSc-87l42zLGDAZcee5ADUNmJpQHNjO51l56KEJhiQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101341-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101339"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101339/Guanylate_binding_proteins_promote_caspase_11_dependent_pyroptosis_in_response_to_cytoplasmic_LPS"><img alt="Research paper thumbnail of Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS" class="work-thumbnail" src="https://attachments.academia-assets.com/73195686/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101339/Guanylate_binding_proteins_promote_caspase_11_dependent_pyroptosis_in_response_to_cytoplasmic_LPS">Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS</a></div><div class="wp-workCard_item"><span>Proceedings of the National Academy of Sciences</span><span>, 2014</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="39bce8b3558921fe6e7a6a6f5bfd16e4" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195686,"asset_id":59101339,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195686/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101339"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101339"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101339; 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The study highlights that Gbp proteins are crucial for the detection of cytoplasmic LPS in macrophages infected with the respiratory pathogen Legionella pneumophila, ultimately leading to cell-autonomous immunity. Experimental evidence demonstrates that Gbp proteins enhance immune responses to both L. pneumophila and other Gram-negative bacteria like Salmonella and E. coli.","ai_title_tag":"Gbp Proteins Induce Caspase-11 Pyroptosis","publication_date":{"day":null,"month":null,"year":2014,"errors":{}},"publication_name":"Proceedings of the National Academy of Sciences"},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101339/Guanylate_binding_proteins_promote_caspase_11_dependent_pyroptosis_in_response_to_cytoplasmic_LPS","translated_internal_url":"","created_at":"2021-10-20T04:19:29.011-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195686,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195686/thumbnails/1.jpg","file_name":"6046.full.pdf","download_url":"https://www.academia.edu/attachments/73195686/download_file","bulk_download_file_name":"Guanylate_binding_proteins_promote_caspa.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195686/6046.full-libre.pdf?1634732267=\u0026response-content-disposition=attachment%3B+filename%3DGuanylate_binding_proteins_promote_caspa.pdf\u0026Expires=1743659393\u0026Signature=ZcFdRgvEpLfnznYyS8kEP~NBA6Keon~a7KHh3BWY8j-9Sr4PZYFTkGmW~pdRluWX0b59rPFTcRnojATYyPiSn7db06CGhygt3Q4zNgWBLFynjSJxKrdqp8vBGJExxgptRnlzJB83kc0ztWVeBUtjMf3eXVzciBUhHqr9q5qY5pF~VDjKGMRk1nEQlIQD04HSgLeAAsz2DvAGnjZ-pZ2PY4sSQwlldj9Y89gE8BlSdmNdW1APE3mXQMSFjxGRkywPCB4MRxwR-LE9QqKIdBl~SJpskwYROTR~iG0u5Wh9dGsIDqrUzUREHs-CgOxNlwdHJXgvf~ojdE-EWZQetOFcOg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Guanylate_binding_proteins_promote_caspase_11_dependent_pyroptosis_in_response_to_cytoplasmic_LPS","translated_slug":"","page_count":6,"language":"en","content_type":"Work","summary":null,"owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195686,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195686/thumbnails/1.jpg","file_name":"6046.full.pdf","download_url":"https://www.academia.edu/attachments/73195686/download_file","bulk_download_file_name":"Guanylate_binding_proteins_promote_caspa.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195686/6046.full-libre.pdf?1634732267=\u0026response-content-disposition=attachment%3B+filename%3DGuanylate_binding_proteins_promote_caspa.pdf\u0026Expires=1743659393\u0026Signature=ZcFdRgvEpLfnznYyS8kEP~NBA6Keon~a7KHh3BWY8j-9Sr4PZYFTkGmW~pdRluWX0b59rPFTcRnojATYyPiSn7db06CGhygt3Q4zNgWBLFynjSJxKrdqp8vBGJExxgptRnlzJB83kc0ztWVeBUtjMf3eXVzciBUhHqr9q5qY5pF~VDjKGMRk1nEQlIQD04HSgLeAAsz2DvAGnjZ-pZ2PY4sSQwlldj9Y89gE8BlSdmNdW1APE3mXQMSFjxGRkywPCB4MRxwR-LE9QqKIdBl~SJpskwYROTR~iG0u5Wh9dGsIDqrUzUREHs-CgOxNlwdHJXgvf~ojdE-EWZQetOFcOg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":50841,"name":"Caspases","url":"https://www.academia.edu/Documents/in/Caspases"},{"id":74780,"name":"Mutation","url":"https://www.academia.edu/Documents/in/Mutation"},{"id":78116,"name":"Legionella pneumophila","url":"https://www.academia.edu/Documents/in/Legionella_pneumophila"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":102637,"name":"Salmonella Typhimurium","url":"https://www.academia.edu/Documents/in/Salmonella_Typhimurium"},{"id":234980,"name":"NADPH oxidase","url":"https://www.academia.edu/Documents/in/NADPH_oxidase"},{"id":335983,"name":"Lipopolysaccharides","url":"https://www.academia.edu/Documents/in/Lipopolysaccharides"},{"id":1166930,"name":"Cytoplasm","url":"https://www.academia.edu/Documents/in/Cytoplasm"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":3464694,"name":"Macrophage activation","url":"https://www.academia.edu/Documents/in/Macrophage_activation"},{"id":3933647,"name":"Legionnaires Disease","url":"https://www.academia.edu/Documents/in/Legionnaires_Disease-1"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101339-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101336"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101336/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins"><img alt="Research paper thumbnail of IRG and GBP Host Resistance Factors Target Aberrant, “Non-self” Vacuoles Characterized by the Missing of “Self” IRGM Proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/73195666/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101336/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins">IRG and GBP Host Resistance Factors Target Aberrant, “Non-self” Vacuoles Characterized by the Missing of “Self” IRGM Proteins</a></div><div class="wp-workCard_item"><span>PLoS Pathogens</span><span>, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with ''non-self'' PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on ''self'' organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="eaa28ecf37ba5679b7c6e28895b7cd9e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195666,"asset_id":59101336,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195666/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101336"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101336"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101336; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101336]").text(description); $(".js-view-count[data-work-id=59101336]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101336; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101336']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "eaa28ecf37ba5679b7c6e28895b7cd9e" } } $('.js-work-strip[data-work-id=59101336]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101336,"title":"IRG and GBP Host Resistance Factors Target Aberrant, “Non-self” Vacuoles Characterized by the Missing of “Self” IRGM Proteins","translated_title":"","metadata":{"publisher":"Public Library of Science (PLoS)","grobid_abstract":"Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with ''non-self'' PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on ''self'' organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.","publication_date":{"day":null,"month":null,"year":2013,"errors":{}},"publication_name":"PLoS Pathogens","grobid_abstract_attachment_id":73195666},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101336/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins","translated_internal_url":"","created_at":"2021-10-20T04:19:28.911-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195666,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195666/thumbnails/1.jpg","file_name":"3be1431048b2f7aa190c3581fdaacbba1c9a.pdf","download_url":"https://www.academia.edu/attachments/73195666/download_file","bulk_download_file_name":"IRG_and_GBP_Host_Resistance_Factors_Targ.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195666/3be1431048b2f7aa190c3581fdaacbba1c9a-libre.pdf?1634732272=\u0026response-content-disposition=attachment%3B+filename%3DIRG_and_GBP_Host_Resistance_Factors_Targ.pdf\u0026Expires=1743659393\u0026Signature=cV2Il0xZMa8ttI3FPiUhb9NvQtZf5KDxSHjLIk~8iPh3VOnU6OK72dzBcm0h69~zWwmhEea8Lexgtk7ExuY2Eq3cgJ~hhtKmZUOT~FgDRJHtf5mF477eGY5PcRsxHRWb3ib1G1mhtOt1vEAtrsXXlcW18zzwqh0VABsFpJuTGUnj82dFp9NPsMcqimHURYpb2C-644urpYfuN59aJlbE18mmXKHzZibJ57w5k7VAceWG5sGmEekh-VRjCdnKncF20-bKkrjs590IybYwaeRODvhrxx2rUsocuQhsO0FeGbr1uZIG02Rv62z~t79k8~YyEgGf~BVw4hFbO3u8gxhgLw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins","translated_slug":"","page_count":16,"language":"en","content_type":"Work","summary":"Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with ''non-self'' PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on ''self'' organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195666,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195666/thumbnails/1.jpg","file_name":"3be1431048b2f7aa190c3581fdaacbba1c9a.pdf","download_url":"https://www.academia.edu/attachments/73195666/download_file","bulk_download_file_name":"IRG_and_GBP_Host_Resistance_Factors_Targ.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195666/3be1431048b2f7aa190c3581fdaacbba1c9a-libre.pdf?1634732272=\u0026response-content-disposition=attachment%3B+filename%3DIRG_and_GBP_Host_Resistance_Factors_Targ.pdf\u0026Expires=1743659393\u0026Signature=cV2Il0xZMa8ttI3FPiUhb9NvQtZf5KDxSHjLIk~8iPh3VOnU6OK72dzBcm0h69~zWwmhEea8Lexgtk7ExuY2Eq3cgJ~hhtKmZUOT~FgDRJHtf5mF477eGY5PcRsxHRWb3ib1G1mhtOt1vEAtrsXXlcW18zzwqh0VABsFpJuTGUnj82dFp9NPsMcqimHURYpb2C-644urpYfuN59aJlbE18mmXKHzZibJ57w5k7VAceWG5sGmEekh-VRjCdnKncF20-bKkrjs590IybYwaeRODvhrxx2rUsocuQhsO0FeGbr1uZIG02Rv62z~t79k8~YyEgGf~BVw4hFbO3u8gxhgLw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology"},{"id":6947,"name":"Medical Microbiology","url":"https://www.academia.edu/Documents/in/Medical_Microbiology"},{"id":13346,"name":"Toxoplasma","url":"https://www.academia.edu/Documents/in/Toxoplasma"},{"id":24706,"name":"Innate immunity","url":"https://www.academia.edu/Documents/in/Innate_immunity"},{"id":34106,"name":"Chlamydia trachomatis","url":"https://www.academia.edu/Documents/in/Chlamydia_trachomatis"},{"id":37798,"name":"Toxoplasmosis","url":"https://www.academia.edu/Documents/in/Toxoplasmosis"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":2428330,"name":"Vacuoles","url":"https://www.academia.edu/Documents/in/Vacuoles"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101336-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101334"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101334/Leishmania_donovani_Isolates_with_Antimony_Resistant_but_Not_Sensitive_Phenotype_Inhibit_Sodium_Antimony_Gluconate_Induced_Dendritic_Cell_Activation"><img alt="Research paper thumbnail of Leishmania donovani Isolates with Antimony-Resistant but Not -Sensitive Phenotype Inhibit Sodium Antimony Gluconate-Induced Dendritic Cell Activation" class="work-thumbnail" src="https://attachments.academia-assets.com/73195785/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101334/Leishmania_donovani_Isolates_with_Antimony_Resistant_but_Not_Sensitive_Phenotype_Inhibit_Sodium_Antimony_Gluconate_Induced_Dendritic_Cell_Activation">Leishmania donovani Isolates with Antimony-Resistant but Not -Sensitive Phenotype Inhibit Sodium Antimony Gluconate-Induced Dendritic Cell Activation</a></div><div class="wp-workCard_item"><span>PLoS Pathogens</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishma...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishmania donovani (LD) infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs) typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (Sb R LD) and antimony-sensitive (Sb S LD) was compared in vitro. Unlike Sb S LD, infection of DCs with Sb R LD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. Sb R LD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-kB pathways. In contrast, Sb S LD failed to block activation of SAG (20 mg/ml)-induced PI3K/AKT pathway; which continued to stimulate NF-kB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with Sb S LD also inhibited SAG (20 mg/ml)-induced activation of PI3K/AKT and NF-kB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 mg/ml. In contrast, Sb R LD inhibited these SAG-induced events regardless of duration of DC exposure to Sb R LD or dose of SAG. Interestingly, the inhibitory effects of isogenic Sb S LD expressing ATP-binding cassette (ABC) transporter MRPA on SAG-induced leishmanicidal effects mimicked that of Sb R LD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-kB was found to transcriptionally regulate expression of murine cglutamylcysteine synthetase heavy-chain (mcGCS hc) gene, presumably an important regulator of antimony resistance. Importantly, Sb R LD but not Sb S LD blocked SAG-induced mcGCS expression in DCs by preventing NF-kB binding to the mcGCS hc promoter. Our findings demonstrate that Sb R LD but not Sb S LD prevents SAG-induced DC activation by suppressing a PI3K-dependent NF-kB pathway and provide the evidence for differential host-pathogen interaction mediated by Sb R LD and Sb S LD.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="862421b26a570e8e306fd29a66f41ea1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195785,"asset_id":59101334,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195785/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101334"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101334"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101334; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101334]").text(description); $(".js-view-count[data-work-id=59101334]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101334; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101334']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "862421b26a570e8e306fd29a66f41ea1" } } $('.js-work-strip[data-work-id=59101334]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101334,"title":"Leishmania donovani Isolates with Antimony-Resistant but Not -Sensitive Phenotype Inhibit Sodium Antimony Gluconate-Induced Dendritic Cell Activation","translated_title":"","metadata":{"publisher":"Public Library of Science (PLoS)","grobid_abstract":"The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishmania donovani (LD) infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs) typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (Sb R LD) and antimony-sensitive (Sb S LD) was compared in vitro. Unlike Sb S LD, infection of DCs with Sb R LD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. Sb R LD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-kB pathways. In contrast, Sb S LD failed to block activation of SAG (20 mg/ml)-induced PI3K/AKT pathway; which continued to stimulate NF-kB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with Sb S LD also inhibited SAG (20 mg/ml)-induced activation of PI3K/AKT and NF-kB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 mg/ml. In contrast, Sb R LD inhibited these SAG-induced events regardless of duration of DC exposure to Sb R LD or dose of SAG. Interestingly, the inhibitory effects of isogenic Sb S LD expressing ATP-binding cassette (ABC) transporter MRPA on SAG-induced leishmanicidal effects mimicked that of Sb R LD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-kB was found to transcriptionally regulate expression of murine cglutamylcysteine synthetase heavy-chain (mcGCS hc) gene, presumably an important regulator of antimony resistance. Importantly, Sb R LD but not Sb S LD blocked SAG-induced mcGCS expression in DCs by preventing NF-kB binding to the mcGCS hc promoter. Our findings demonstrate that Sb R LD but not Sb S LD prevents SAG-induced DC activation by suppressing a PI3K-dependent NF-kB pathway and provide the evidence for differential host-pathogen interaction mediated by Sb R LD and Sb S LD.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"PLoS Pathogens","grobid_abstract_attachment_id":73195785},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101334/Leishmania_donovani_Isolates_with_Antimony_Resistant_but_Not_Sensitive_Phenotype_Inhibit_Sodium_Antimony_Gluconate_Induced_Dendritic_Cell_Activation","translated_internal_url":"","created_at":"2021-10-20T04:19:28.806-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195785,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195785/thumbnails/1.jpg","file_name":"11d88a9f0220f1a1f03e83345a24b0808f36.pdf","download_url":"https://www.academia.edu/attachments/73195785/download_file","bulk_download_file_name":"Leishmania_donovani_Isolates_with_Antimo.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195785/11d88a9f0220f1a1f03e83345a24b0808f36-libre.pdf?1634732263=\u0026response-content-disposition=attachment%3B+filename%3DLeishmania_donovani_Isolates_with_Antimo.pdf\u0026Expires=1743659393\u0026Signature=hBLRMmdYDfnAtb35qvE1pY627Sb16T4vY9P8j4gSShfCGO63WtqzGf~VqN4V6F0-11s62~75dBuqtLnCvJxIRJBlFc1FSRDtVrvqiuMMVCkVvoS~nBUb4fylqWeje9JED3ETShIuVMMoTbivEdtvUz2cZvhBIvBwYRbVWu6PoQ62BJKlIV9dGYqNk16WLluw95p10BUmLBcILYPz2YJEcogZIcnByXRJrmu2FwFJNyooBHxQ-r6TTOAgPv3rQBfaCq2JKCm7CSMc71y38g6cLKz5veTi6ls0xHguD-dbQhP7hzG~qqf3Kkpok1EgaExzEAk9DQwMp9monyVls7GHyw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Leishmania_donovani_Isolates_with_Antimony_Resistant_but_Not_Sensitive_Phenotype_Inhibit_Sodium_Antimony_Gluconate_Induced_Dendritic_Cell_Activation","translated_slug":"","page_count":21,"language":"en","content_type":"Work","summary":"The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishmania donovani (LD) infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs) typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (Sb R LD) and antimony-sensitive (Sb S LD) was compared in vitro. Unlike Sb S LD, infection of DCs with Sb R LD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. Sb R LD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-kB pathways. In contrast, Sb S LD failed to block activation of SAG (20 mg/ml)-induced PI3K/AKT pathway; which continued to stimulate NF-kB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with Sb S LD also inhibited SAG (20 mg/ml)-induced activation of PI3K/AKT and NF-kB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 mg/ml. In contrast, Sb R LD inhibited these SAG-induced events regardless of duration of DC exposure to Sb R LD or dose of SAG. Interestingly, the inhibitory effects of isogenic Sb S LD expressing ATP-binding cassette (ABC) transporter MRPA on SAG-induced leishmanicidal effects mimicked that of Sb R LD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-kB was found to transcriptionally regulate expression of murine cglutamylcysteine synthetase heavy-chain (mcGCS hc) gene, presumably an important regulator of antimony resistance. Importantly, Sb R LD but not Sb S LD blocked SAG-induced mcGCS expression in DCs by preventing NF-kB binding to the mcGCS hc promoter. Our findings demonstrate that Sb R LD but not Sb S LD prevents SAG-induced DC activation by suppressing a PI3K-dependent NF-kB pathway and provide the evidence for differential host-pathogen interaction mediated by Sb R LD and Sb S LD.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195785,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195785/thumbnails/1.jpg","file_name":"11d88a9f0220f1a1f03e83345a24b0808f36.pdf","download_url":"https://www.academia.edu/attachments/73195785/download_file","bulk_download_file_name":"Leishmania_donovani_Isolates_with_Antimo.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195785/11d88a9f0220f1a1f03e83345a24b0808f36-libre.pdf?1634732263=\u0026response-content-disposition=attachment%3B+filename%3DLeishmania_donovani_Isolates_with_Antimo.pdf\u0026Expires=1743659393\u0026Signature=hBLRMmdYDfnAtb35qvE1pY627Sb16T4vY9P8j4gSShfCGO63WtqzGf~VqN4V6F0-11s62~75dBuqtLnCvJxIRJBlFc1FSRDtVrvqiuMMVCkVvoS~nBUb4fylqWeje9JED3ETShIuVMMoTbivEdtvUz2cZvhBIvBwYRbVWu6PoQ62BJKlIV9dGYqNk16WLluw95p10BUmLBcILYPz2YJEcogZIcnByXRJrmu2FwFJNyooBHxQ-r6TTOAgPv3rQBfaCq2JKCm7CSMc71y38g6cLKz5veTi6ls0xHguD-dbQhP7hzG~qqf3Kkpok1EgaExzEAk9DQwMp9monyVls7GHyw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology"},{"id":6947,"name":"Medical Microbiology","url":"https://www.academia.edu/Documents/in/Medical_Microbiology"},{"id":27784,"name":"Gene expression","url":"https://www.academia.edu/Documents/in/Gene_expression"},{"id":35539,"name":"Dendritic Cells","url":"https://www.academia.edu/Documents/in/Dendritic_Cells"},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":102583,"name":"Drug Resistance","url":"https://www.academia.edu/Documents/in/Drug_Resistance"},{"id":128006,"name":"Sodium Antimony Gluconate","url":"https://www.academia.edu/Documents/in/Sodium_Antimony_Gluconate"},{"id":142138,"name":"Host-parasite interactions","url":"https://www.academia.edu/Documents/in/Host-parasite_interactions"},{"id":153279,"name":"Dendritic cell","url":"https://www.academia.edu/Documents/in/Dendritic_cell"},{"id":213897,"name":"Phenotype","url":"https://www.academia.edu/Documents/in/Phenotype"},{"id":325838,"name":"Host Pathogen Interaction","url":"https://www.academia.edu/Documents/in/Host_Pathogen_Interaction-1"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin"},{"id":2239983,"name":"Glutamate Cysteine Ligase","url":"https://www.academia.edu/Documents/in/Glutamate_Cysteine_Ligase"},{"id":2971099,"name":"Heavy Chain","url":"https://www.academia.edu/Documents/in/Heavy_Chain"},{"id":3214915,"name":"Cricetinae","url":"https://www.academia.edu/Documents/in/Cricetinae"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101334-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101331"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101331/Activation_of_macrophages_and_lymphocytes_by_methylglyoxal_against_tumor_cells_in_the_host"><img alt="Research paper thumbnail of Activation of macrophages and lymphocytes by methylglyoxal against tumor cells in the host" class="work-thumbnail" src="https://attachments.academia-assets.com/73195674/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101331/Activation_of_macrophages_and_lymphocytes_by_methylglyoxal_against_tumor_cells_in_the_host">Activation of macrophages and lymphocytes by methylglyoxal against tumor cells in the host</a></div><div class="wp-workCard_item"><span>International Immunopharmacology</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular p...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular processes. In particular, it can act selectively against malignant cells. The study described herein was to investigate whether methylglyoxal can enhance the non-specific immunity of the host against tumor cells. Methylglyoxal increased the number of macrophages in the peritoneal cavity of both normal and tumor-bearing mice. It also elevated the phagocytic capacity of macrophages in both these groups of animals. This activation of macrophages was brought about by increased production of Reactive Oxygen Intermediates (ROIs) and Reactive Nitrogen Intermediates (RNIs). The possible mechanism for the production of ROIs and RNIs can be attributed to stimulation of the respiratory burst enzyme NADPH oxidase and iNOS, respectively. IFN-γ, which is a regulatory molecule of iNOS pathway also showed an elevated level by methylglyoxal. TNF-α, which is an important cytokine for oxygen independent killing by macrophage also increased by methylglyoxal in both tumor-bearing and non tumor-bearing animals. Methylglyoxal also played a role in the proliferation and cytotoxicity of splenic lymphocytes. In short, it can be concluded that methylglyoxal profoundly stimulates the immune system against tumor cells.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="9c81bd0f604b1cbe1b25d28af2c6a282" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195674,"asset_id":59101331,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195674/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101331"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101331"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101331; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101331]").text(description); $(".js-view-count[data-work-id=59101331]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101331; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101331']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "9c81bd0f604b1cbe1b25d28af2c6a282" } } $('.js-work-strip[data-work-id=59101331]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101331,"title":"Activation of macrophages and lymphocytes by methylglyoxal against tumor cells in the host","translated_title":"","metadata":{"publisher":"Elsevier BV","ai_title_tag":"Methylglyoxal Enhances Immune Response Against Tumors","grobid_abstract":"Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular processes. In particular, it can act selectively against malignant cells. The study described herein was to investigate whether methylglyoxal can enhance the non-specific immunity of the host against tumor cells. Methylglyoxal increased the number of macrophages in the peritoneal cavity of both normal and tumor-bearing mice. It also elevated the phagocytic capacity of macrophages in both these groups of animals. This activation of macrophages was brought about by increased production of Reactive Oxygen Intermediates (ROIs) and Reactive Nitrogen Intermediates (RNIs). The possible mechanism for the production of ROIs and RNIs can be attributed to stimulation of the respiratory burst enzyme NADPH oxidase and iNOS, respectively. IFN-γ, which is a regulatory molecule of iNOS pathway also showed an elevated level by methylglyoxal. TNF-α, which is an important cytokine for oxygen independent killing by macrophage also increased by methylglyoxal in both tumor-bearing and non tumor-bearing animals. Methylglyoxal also played a role in the proliferation and cytotoxicity of splenic lymphocytes. In short, it can be concluded that methylglyoxal profoundly stimulates the immune system against tumor cells.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"International Immunopharmacology","grobid_abstract_attachment_id":73195674},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101331/Activation_of_macrophages_and_lymphocytes_by_methylglyoxal_against_tumor_cells_in_the_host","translated_internal_url":"","created_at":"2021-10-20T04:19:28.652-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195674,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195674/thumbnails/1.jpg","file_name":"j.intimp.2008.06.00520211020-1303-15cc4vl.pdf","download_url":"https://www.academia.edu/attachments/73195674/download_file","bulk_download_file_name":"Activation_of_macrophages_and_lymphocyte.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195674/j.intimp.2008.06.00520211020-1303-15cc4vl-libre.pdf?1634732267=\u0026response-content-disposition=attachment%3B+filename%3DActivation_of_macrophages_and_lymphocyte.pdf\u0026Expires=1743659393\u0026Signature=JeP6v8hoRiYRxf2v1Kkn-XUtNb~6wY8uw15KN2zwGPIm8cAETi2DTXt-5CNvAjJTFE~rMfTC6KTWLjbgXQ8gzLzE8Z43ZR~tGdWMxJe2abWs-Eg9z3O1bsYoPekUa08dayoxC4O91TEwDJWTcdfjRVY2C9GFbyIgLj~jKsV~ZBpCjAblvBuBVtKGcnvNx2H8OoW25ucOq-GIQs~b7ATbr449CYiyRPFImcPmprEiDe4sGcooB~MdNPUqC7xOjmOxpMENNzeF-3hbBDps~kIjXzU7o-Io5MfB7hb~GjiGTtJy2VxcxJshjWScNoQrSYFLLA0RQintldYrsM7tzbDOsw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Activation_of_macrophages_and_lymphocytes_by_methylglyoxal_against_tumor_cells_in_the_host","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular processes. In particular, it can act selectively against malignant cells. The study described herein was to investigate whether methylglyoxal can enhance the non-specific immunity of the host against tumor cells. Methylglyoxal increased the number of macrophages in the peritoneal cavity of both normal and tumor-bearing mice. It also elevated the phagocytic capacity of macrophages in both these groups of animals. This activation of macrophages was brought about by increased production of Reactive Oxygen Intermediates (ROIs) and Reactive Nitrogen Intermediates (RNIs). The possible mechanism for the production of ROIs and RNIs can be attributed to stimulation of the respiratory burst enzyme NADPH oxidase and iNOS, respectively. IFN-γ, which is a regulatory molecule of iNOS pathway also showed an elevated level by methylglyoxal. TNF-α, which is an important cytokine for oxygen independent killing by macrophage also increased by methylglyoxal in both tumor-bearing and non tumor-bearing animals. Methylglyoxal also played a role in the proliferation and cytotoxicity of splenic lymphocytes. In short, it can be concluded that methylglyoxal profoundly stimulates the immune system against tumor cells.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195674,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195674/thumbnails/1.jpg","file_name":"j.intimp.2008.06.00520211020-1303-15cc4vl.pdf","download_url":"https://www.academia.edu/attachments/73195674/download_file","bulk_download_file_name":"Activation_of_macrophages_and_lymphocyte.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195674/j.intimp.2008.06.00520211020-1303-15cc4vl-libre.pdf?1634732267=\u0026response-content-disposition=attachment%3B+filename%3DActivation_of_macrophages_and_lymphocyte.pdf\u0026Expires=1743659393\u0026Signature=JeP6v8hoRiYRxf2v1Kkn-XUtNb~6wY8uw15KN2zwGPIm8cAETi2DTXt-5CNvAjJTFE~rMfTC6KTWLjbgXQ8gzLzE8Z43ZR~tGdWMxJe2abWs-Eg9z3O1bsYoPekUa08dayoxC4O91TEwDJWTcdfjRVY2C9GFbyIgLj~jKsV~ZBpCjAblvBuBVtKGcnvNx2H8OoW25ucOq-GIQs~b7ATbr449CYiyRPFImcPmprEiDe4sGcooB~MdNPUqC7xOjmOxpMENNzeF-3hbBDps~kIjXzU7o-Io5MfB7hb~GjiGTtJy2VxcxJshjWScNoQrSYFLLA0RQintldYrsM7tzbDOsw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":26699,"name":"Immunopharmacology","url":"https://www.academia.edu/Documents/in/Immunopharmacology"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":118793,"name":"Sarcoma","url":"https://www.academia.edu/Documents/in/Sarcoma"},{"id":231661,"name":"Enzyme","url":"https://www.academia.edu/Documents/in/Enzyme"},{"id":234980,"name":"NADPH oxidase","url":"https://www.academia.edu/Documents/in/NADPH_oxidase"},{"id":324154,"name":"Immune system","url":"https://www.academia.edu/Documents/in/Immune_system"},{"id":474029,"name":"Tumor necrosis factor-alpha","url":"https://www.academia.edu/Documents/in/Tumor_necrosis_factor-alpha"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation"},{"id":868560,"name":"Lymphocytes","url":"https://www.academia.edu/Documents/in/Lymphocytes"},{"id":1212103,"name":"Antineoplastic Agents","url":"https://www.academia.edu/Documents/in/Antineoplastic_Agents"},{"id":1455811,"name":"Superoxides","url":"https://www.academia.edu/Documents/in/Superoxides"},{"id":1626171,"name":"Respiratory Burst","url":"https://www.academia.edu/Documents/in/Respiratory_Burst"},{"id":1654024,"name":"Nitrites","url":"https://www.academia.edu/Documents/in/Nitrites"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":3464694,"name":"Macrophage activation","url":"https://www.academia.edu/Documents/in/Macrophage_activation"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101331-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101328"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101328/Designing_Therapies_against_Experimental_Visceral_Leishmaniasis_by_Modulating_the_Membrane_Fluidity_of_Antigen_Presenting_Cells"><img alt="Research paper thumbnail of Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells" class="work-thumbnail" src="https://attachments.academia-assets.com/73195787/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101328/Designing_Therapies_against_Experimental_Visceral_Leishmaniasis_by_Modulating_the_Membrane_Fluidity_of_Antigen_Presenting_Cells">Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells</a></div><div class="wp-workCard_item"><span>Infection and Immunity</span><span>, 2009</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The membrane fluidity of antigen-presenting cells (APCs) has a significant bearing on T-cell-stim...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The membrane fluidity of antigen-presenting cells (APCs) has a significant bearing on T-cell-stimulating ability and is dependent on the cholesterol content of the membrane. The relationship, if any, between membrane fluidity and defective cell-mediated immunity in visceral leishmaniasis has been investigated. Systemic administration of cholesterol by liposome delivery (cholesterol liposomes) in Leishmania donovani -infected hamsters was found to cure the infection. Splenic macrophages as a prototype of APCs in infected hamsters had decreased membrane cholesterol and an inability to drive T cells, which was corrected by cholesterol liposome treatment. The effect was cholesterol specific because liposomes made up of the analogue 4-cholesten-3-one provided almost no protection. Infection led to increases in interleukin-10 (IL-10), transforming growth factor beta, and IL-4 signals and concomitant decreases in gamma interferon (IFN-γ), tumor necrosis factor alpha, and inducible NO synth...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="0f85d6909de9cbe9281d5adec4553d79" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195787,"asset_id":59101328,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195787/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101328"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101328"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101328; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101328]").text(description); $(".js-view-count[data-work-id=59101328]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101328; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101328']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "0f85d6909de9cbe9281d5adec4553d79" } } $('.js-work-strip[data-work-id=59101328]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101328,"title":"Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells","translated_title":"","metadata":{"abstract":"The membrane fluidity of antigen-presenting cells (APCs) has a significant bearing on T-cell-stimulating ability and is dependent on the cholesterol content of the membrane. The relationship, if any, between membrane fluidity and defective cell-mediated immunity in visceral leishmaniasis has been investigated. Systemic administration of cholesterol by liposome delivery (cholesterol liposomes) in Leishmania donovani -infected hamsters was found to cure the infection. Splenic macrophages as a prototype of APCs in infected hamsters had decreased membrane cholesterol and an inability to drive T cells, which was corrected by cholesterol liposome treatment. The effect was cholesterol specific because liposomes made up of the analogue 4-cholesten-3-one provided almost no protection. 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Splenic macrophages as a prototype of APCs in infected hamsters had decreased membrane cholesterol and an inability to drive T cells, which was corrected by cholesterol liposome treatment. The effect was cholesterol specific because liposomes made up of the analogue 4-cholesten-3-one provided almost no protection. 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Infection led to increases in interleukin-10 (IL-10), transforming growth factor beta, and IL-4 signals and concomitant decreases in gamma interferon (IFN-γ), tumor necrosis factor alpha, and inducible NO synth...","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195787,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195787/thumbnails/1.jpg","file_name":"2330.pdf","download_url":"https://www.academia.edu/attachments/73195787/download_file","bulk_download_file_name":"Designing_Therapies_against_Experimental.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195787/2330-libre.pdf?1634732260=\u0026response-content-disposition=attachment%3B+filename%3DDesigning_Therapies_against_Experimental.pdf\u0026Expires=1743659393\u0026Signature=U513KEQbCPL5rJYbxYOxu-LjaEZKv97l2Uv1BFdEZ-4uKbxIzKXHpmeoXQP-anSsMf66OrNEC6fmd-RchXDUm1ubchVOzEPNQ6h0eO0O2rHW8JIKCYnrAlgnpzI0Ym0-WReY5764VIwmUn6AxFV~yBp~VqVSwReu0FNVm3pYbqOcW0wejBxo6zr-wIYIODWPOVxQMY512YcIFTpM2xcqNy-4mXts17s5MWy95QKcBGDXA~nfVRyFs~2j~08-Pojmpedtlepecqwd24zRKq8jjDiVEhui~-64M7juLndRd58RL8KY0XvoM1tNS2CFySPBfOE~e1-G7I3RNuAgwuu9qg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":2702,"name":"Immune response","url":"https://www.academia.edu/Documents/in/Immune_response"},{"id":9111,"name":"Cytokines","url":"https://www.academia.edu/Documents/in/Cytokines"},{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":19849,"name":"Leishmania","url":"https://www.academia.edu/Documents/in/Leishmania"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":48758,"name":"Infection and immunity","url":"https://www.academia.edu/Documents/in/Infection_and_immunity"},{"id":82978,"name":"Reactive Oxygen Species","url":"https://www.academia.edu/Documents/in/Reactive_Oxygen_Species"},{"id":90514,"name":"Cholesterol","url":"https://www.academia.edu/Documents/in/Cholesterol"},{"id":93922,"name":"Nitric oxide","url":"https://www.academia.edu/Documents/in/Nitric_oxide"},{"id":109739,"name":"Infection","url":"https://www.academia.edu/Documents/in/Infection"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":951344,"name":"Growth Factor","url":"https://www.academia.edu/Documents/in/Growth_Factor"},{"id":1426712,"name":"Immunoglobulin","url":"https://www.academia.edu/Documents/in/Immunoglobulin"},{"id":1465015,"name":"Membrane Fluidity","url":"https://www.academia.edu/Documents/in/Membrane_Fluidity"},{"id":1792514,"name":"Antigen presenting cells","url":"https://www.academia.edu/Documents/in/Antigen_presenting_cells"},{"id":2468093,"name":"Cell Membrane","url":"https://www.academia.edu/Documents/in/Cell_Membrane"},{"id":3196500,"name":"Tumor necrosis factor","url":"https://www.academia.edu/Documents/in/Tumor_necrosis_factor"},{"id":3214915,"name":"Cricetinae","url":"https://www.academia.edu/Documents/in/Cricetinae"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101328-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101326"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101326/Hybrid_Cell_Vaccination_Resolves_Leishmania_donovani_Infection_by_Eliciting_a_Strong_CD8_Cytotoxic_T_Lymphocyte_Response_with_Concomitant_Suppression_of_Interleukin_10_IL_10_but_Not_IL_4_or_IL_13"><img alt="Research paper thumbnail of Hybrid Cell Vaccination Resolves Leishmania donovani Infection by Eliciting a Strong CD8+ Cytotoxic T-Lymphocyte Response with Concomitant Suppression of Interleukin-10 (IL-10) but Not IL-4 or IL-13" class="work-thumbnail" src="https://attachments.academia-assets.com/73195783/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101326/Hybrid_Cell_Vaccination_Resolves_Leishmania_donovani_Infection_by_Eliciting_a_Strong_CD8_Cytotoxic_T_Lymphocyte_Response_with_Concomitant_Suppression_of_Interleukin_10_IL_10_but_Not_IL_4_or_IL_13">Hybrid Cell Vaccination Resolves Leishmania donovani Infection by Eliciting a Strong CD8+ Cytotoxic T-Lymphocyte Response with Concomitant Suppression of Interleukin-10 (IL-10) but Not IL-4 or IL-13</a></div><div class="wp-workCard_item"><span>Infection and Immunity</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">There is an acute dearth of therapeutic interventions against visceral leishmaniasis that is requ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">There is an acute dearth of therapeutic interventions against visceral leishmaniasis that is required to restore an established defective cell-mediated immune response. Hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. We implemented hybrid cell vaccination therapy in Leishmania donovani-infected BALB/c mice by electrofusing dominant Leishmania antigen kinetoplastid membrane protein 11 (KMP-11)-transfected bone marrow-derived macrophages from BALB/c mice with allogeneic bone marrow-derived dendritic cells from C57BL/6 mice. Hybrid cell vaccine (HCV) cleared the splenic and hepatic parasite burden, eliciting KMP-11-specific major histocompatibility complex class I-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses. Moreover, splenic lymphocytes of HCV-treated mice not only showed the enhancement of gamma interferon but also marked an elevated expression of the Th2 cytokines i...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="618f701907081dd5bb3f724505821fc0" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195783,"asset_id":59101326,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195783/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101326"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101326"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101326; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101326]").text(description); $(".js-view-count[data-work-id=59101326]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101326; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101326']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "618f701907081dd5bb3f724505821fc0" } } $('.js-work-strip[data-work-id=59101326]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101326,"title":"Hybrid Cell Vaccination Resolves Leishmania donovani Infection by Eliciting a Strong CD8+ Cytotoxic T-Lymphocyte Response with Concomitant Suppression of Interleukin-10 (IL-10) but Not IL-4 or IL-13","translated_title":"","metadata":{"abstract":"There is an acute dearth of therapeutic interventions against visceral leishmaniasis that is required to restore an established defective cell-mediated immune response. Hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. We implemented hybrid cell vaccination therapy in Leishmania donovani-infected BALB/c mice by electrofusing dominant Leishmania antigen kinetoplastid membrane protein 11 (KMP-11)-transfected bone marrow-derived macrophages from BALB/c mice with allogeneic bone marrow-derived dendritic cells from C57BL/6 mice. Hybrid cell vaccine (HCV) cleared the splenic and hepatic parasite burden, eliciting KMP-11-specific major histocompatibility complex class I-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses. Moreover, splenic lymphocytes of HCV-treated mice not only showed the enhancement of gamma interferon but also marked an elevated expression of the Th2 cytokines i...","publisher":"American Society for Microbiology","ai_title_tag":"Hybrid Cell Vaccination against Leishmania","publication_date":{"day":null,"month":null,"year":2007,"errors":{}},"publication_name":"Infection and Immunity"},"translated_abstract":"There is an acute dearth of therapeutic interventions against visceral leishmaniasis that is required to restore an established defective cell-mediated immune response. Hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. We implemented hybrid cell vaccination therapy in Leishmania donovani-infected BALB/c mice by electrofusing dominant Leishmania antigen kinetoplastid membrane protein 11 (KMP-11)-transfected bone marrow-derived macrophages from BALB/c mice with allogeneic bone marrow-derived dendritic cells from C57BL/6 mice. Hybrid cell vaccine (HCV) cleared the splenic and hepatic parasite burden, eliciting KMP-11-specific major histocompatibility complex class I-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses. 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Hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. We implemented hybrid cell vaccination therapy in Leishmania donovani-infected BALB/c mice by electrofusing dominant Leishmania antigen kinetoplastid membrane protein 11 (KMP-11)-transfected bone marrow-derived macrophages from BALB/c mice with allogeneic bone marrow-derived dendritic cells from C57BL/6 mice. Hybrid cell vaccine (HCV) cleared the splenic and hepatic parasite burden, eliciting KMP-11-specific major histocompatibility complex class I-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101326-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101323"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101323/Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_%CE%B3_to_IL_10_ratio"><img alt="Research paper thumbnail of Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio" class="work-thumbnail" src="https://attachments.academia-assets.com/73195813/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101323/Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_%CE%B3_to_IL_10_ratio">Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio</a></div><div class="wp-workCard_item"><span>Experimental Parasitology</span><span>, 2009</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and t...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O 2) 2 (H 2 O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb R) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-c and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-c inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="835de0aeffe0c9db846396e9e10541a7" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195813,"asset_id":59101323,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195813/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101323"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101323"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101323; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101323]").text(description); $(".js-view-count[data-work-id=59101323]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101323; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101323']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "835de0aeffe0c9db846396e9e10541a7" } } $('.js-work-strip[data-work-id=59101323]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101323,"title":"Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio","translated_title":"","metadata":{"publisher":"Elsevier BV","ai_title_tag":"SAG-PV6 Combo Treats Antimony Resistant Leishmaniasis","grobid_abstract":"We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O 2) 2 (H 2 O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb R) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-c and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-c inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.","publication_date":{"day":null,"month":null,"year":2009,"errors":{}},"publication_name":"Experimental Parasitology","grobid_abstract_attachment_id":73195813},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101323/Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_%CE%B3_to_IL_10_ratio","translated_internal_url":"","created_at":"2021-10-20T04:19:28.348-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195813,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195813/thumbnails/1.jpg","file_name":"j.exppara.2009.02.00120211020-1300-5rueab.pdf","download_url":"https://www.academia.edu/attachments/73195813/download_file","bulk_download_file_name":"Sub_optimal_dose_of_Sodium_Antimony_Gluc.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195813/j.exppara.2009.02.00120211020-1300-5rueab-libre.pdf?1634732259=\u0026response-content-disposition=attachment%3B+filename%3DSub_optimal_dose_of_Sodium_Antimony_Gluc.pdf\u0026Expires=1743659393\u0026Signature=KIiW~rhxwQDr9DgO49heGmIpdGzc~zl5LV52tnN~lcVctjVLsGdzeqvuSo-wLWPe2NI66dQT86-llJYmp14wQxARX~OZWynislO5lVWj-Qs-23qhxEA4c6diNWbta7NTVYAACWeCJw7yr0QagxlrM1XyJ6i5oIaATrG7lNBJog7kbuClTHxcPsMGJcp7Y4rSp9Chki7HArm5iPWSchVQ9jxHhrcsoXhK9hIRbhBT4MlHSsj8W8D8GGQlJMZ5eCTtvmzf5MWSiJykqzdl5KumKyDcTqT5wu2eWFQmmGBmUahRL6-Dkv3np6K-lesbxlJpOIuGe6MWya~AZw2JcUZwFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_γ_to_IL_10_ratio","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O 2) 2 (H 2 O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb R) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-c and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-c inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195813,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195813/thumbnails/1.jpg","file_name":"j.exppara.2009.02.00120211020-1300-5rueab.pdf","download_url":"https://www.academia.edu/attachments/73195813/download_file","bulk_download_file_name":"Sub_optimal_dose_of_Sodium_Antimony_Gluc.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195813/j.exppara.2009.02.00120211020-1300-5rueab-libre.pdf?1634732259=\u0026response-content-disposition=attachment%3B+filename%3DSub_optimal_dose_of_Sodium_Antimony_Gluc.pdf\u0026Expires=1743659393\u0026Signature=KIiW~rhxwQDr9DgO49heGmIpdGzc~zl5LV52tnN~lcVctjVLsGdzeqvuSo-wLWPe2NI66dQT86-llJYmp14wQxARX~OZWynislO5lVWj-Qs-23qhxEA4c6diNWbta7NTVYAACWeCJw7yr0QagxlrM1XyJ6i5oIaATrG7lNBJog7kbuClTHxcPsMGJcp7Y4rSp9Chki7HArm5iPWSchVQ9jxHhrcsoXhK9hIRbhBT4MlHSsj8W8D8GGQlJMZ5eCTtvmzf5MWSiJykqzdl5KumKyDcTqT5wu2eWFQmmGBmUahRL6-Dkv3np6K-lesbxlJpOIuGe6MWya~AZw2JcUZwFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":49018,"name":"Spleen","url":"https://www.academia.edu/Documents/in/Spleen"},{"id":53307,"name":"Experimental parasitology","url":"https://www.academia.edu/Documents/in/Experimental_parasitology"},{"id":71437,"name":"Liver","url":"https://www.academia.edu/Documents/in/Liver"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":93922,"name":"Nitric oxide","url":"https://www.academia.edu/Documents/in/Nitric_oxide"},{"id":94271,"name":"Parasite","url":"https://www.academia.edu/Documents/in/Parasite"},{"id":102583,"name":"Drug Resistance","url":"https://www.academia.edu/Documents/in/Drug_Resistance"},{"id":128006,"name":"Sodium Antimony Gluconate","url":"https://www.academia.edu/Documents/in/Sodium_Antimony_Gluconate"},{"id":203750,"name":"Dose","url":"https://www.academia.edu/Documents/in/Dose"},{"id":238630,"name":"Experimental Infection","url":"https://www.academia.edu/Documents/in/Experimental_Infection"},{"id":280237,"name":"T lymphocytes","url":"https://www.academia.edu/Documents/in/T_lymphocytes"},{"id":329844,"name":"Experimental","url":"https://www.academia.edu/Documents/in/Experimental"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"},{"id":1455811,"name":"Superoxides","url":"https://www.academia.edu/Documents/in/Superoxides"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":3094724,"name":"Peroxides","url":"https://www.academia.edu/Documents/in/Peroxides"},{"id":3214915,"name":"Cricetinae","url":"https://www.academia.edu/Documents/in/Cricetinae"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101323-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101321"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101321/Radio_attenuated_leishmanial_parasites_as_immunoprophylactic_agent_against_experimental_murine_visceral_leishmaniasis"><img alt="Research paper thumbnail of Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis" class="work-thumbnail" src="https://attachments.academia-assets.com/73195682/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101321/Radio_attenuated_leishmanial_parasites_as_immunoprophylactic_agent_against_experimental_murine_visceral_leishmaniasis">Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis</a></div><div class="wp-workCard_item"><span>Experimental Parasitology</span><span>, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The present study intends to evaluate the role of radio-attenuated leishmania parasites as immuno...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The present study intends to evaluate the role of radio-attenuated leishmania parasites as immunoprophylactic agents for experimental murine visceral leishmaniasis. BALB/c mice were immunized with gamma (c)-irradiated Leishmania donovani. A second immunization was given after 15 days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimental groups. It was observed that BALB/c mice having prior immunization with radio-attenuated parasites showed protection against L. donovani infection through higher expression of Th1 cytokines and suppression of Th2 cytokines along with the generation of protective free radicals. The group of mice without prior priming with radio-attenuated parasites surrendered to the disease. Thus it can be concluded that radio-attenuated L. donovani may be used for.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="4fa1fd854a5c56926c25bcd99017fdec" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195682,"asset_id":59101321,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195682/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101321"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101321"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101321; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101321]").text(description); $(".js-view-count[data-work-id=59101321]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101321; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101321']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "4fa1fd854a5c56926c25bcd99017fdec" } } $('.js-work-strip[data-work-id=59101321]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101321,"title":"Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis","translated_title":"","metadata":{"publisher":"Elsevier BV","ai_title_tag":"Immunization with Radio-Attenuated Leishmania Against Visceral Leishmaniasis","grobid_abstract":"The present study intends to evaluate the role of radio-attenuated leishmania parasites as immunoprophylactic agents for experimental murine visceral leishmaniasis. BALB/c mice were immunized with gamma (c)-irradiated Leishmania donovani. A second immunization was given after 15 days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimental groups. It was observed that BALB/c mice having prior immunization with radio-attenuated parasites showed protection against L. donovani infection through higher expression of Th1 cytokines and suppression of Th2 cytokines along with the generation of protective free radicals. The group of mice without prior priming with radio-attenuated parasites surrendered to the disease. 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BALB/c mice were immunized with gamma (c)-irradiated Leishmania donovani. A second immunization was given after 15 days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimental groups. It was observed that BALB/c mice having prior immunization with radio-attenuated parasites showed protection against L. donovani infection through higher expression of Th1 cytokines and suppression of Th2 cytokines along with the generation of protective free radicals. The group of mice without prior priming with radio-attenuated parasites surrendered to the disease. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101321-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101113"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101113/The_E2_Like_Conjugation_Enzyme_Atg3_Promotes_Binding_of_IRG_and_Gbp_Proteins_to_Chlamydia_and_Toxoplasma_Containing_Vacuoles_and_Host_Resistance"><img alt="Research paper thumbnail of The E2-Like Conjugation Enzyme Atg3 Promotes Binding of IRG and Gbp Proteins to Chlamydia- and Toxoplasma-Containing Vacuoles and Host Resistance" class="work-thumbnail" src="https://attachments.academia-assets.com/73195502/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101113/The_E2_Like_Conjugation_Enzyme_Atg3_Promotes_Binding_of_IRG_and_Gbp_Proteins_to_Chlamydia_and_Toxoplasma_Containing_Vacuoles_and_Host_Resistance">The E2-Like Conjugation Enzyme Atg3 Promotes Binding of IRG and Gbp Proteins to Chlamydia- and Toxoplasma-Containing Vacuoles and Host Resistance</a></div><div class="wp-workCard_item"><span>PLoS ONE</span><span>, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathog...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathogen Toxoplasma gondii is controlled by two families of Interferon (IFN)-inducible GTPases: Immunity Related GTPases (IRGs) and Guanylate binding proteins (Gbps). Members of these two GTPase families associate with pathogen-containing vacuoles (PVs) and solicit antimicrobial resistance pathways specifically to the intracellular site of infection. The proper delivery of IRG and Gbp proteins to PVs requires the autophagy factor Atg5. Atg5 is part of a protein complex that facilitates the transfer of the ubiquitin-like protein Atg8 from the E2-like conjugation enzyme Atg3 to the lipid phosphatidylethanolamine. Here, we show that Atg3 expression, similar to Atg5 expression, is required for IRG and Gbp proteins to dock to PVs. We further demonstrate that expression of a dominant-active, GTP-locked IRG protein variant rescues the PV targeting defect of Atg3and Atg5-deficient cells, suggesting a possible role for Atg proteins in the activation of IRG proteins. Lastly, we show that IFN-induced cell-autonomous resistance to C. trachomatis infections in mouse cells depends not only on Atg5 and IRG proteins, as previously demonstrated, but also requires the expression of Atg3 and Gbp proteins. These findings provide a foundation for a better understanding of IRG-and Gbp-dependent cell-autonomous resistance and its regulation by Atg proteins.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="06b2bc702bf795b86bd4a61d8c545afa" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195502,"asset_id":59101113,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195502/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101113"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101113"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101113; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101113]").text(description); $(".js-view-count[data-work-id=59101113]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101113; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101113']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "06b2bc702bf795b86bd4a61d8c545afa" } } $('.js-work-strip[data-work-id=59101113]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101113,"title":"The E2-Like Conjugation Enzyme Atg3 Promotes Binding of IRG and Gbp Proteins to Chlamydia- and Toxoplasma-Containing Vacuoles and Host Resistance","translated_title":"","metadata":{"publisher":"Public Library of Science (PLoS)","grobid_abstract":"Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathogen Toxoplasma gondii is controlled by two families of Interferon (IFN)-inducible GTPases: Immunity Related GTPases (IRGs) and Guanylate binding proteins (Gbps). Members of these two GTPase families associate with pathogen-containing vacuoles (PVs) and solicit antimicrobial resistance pathways specifically to the intracellular site of infection. The proper delivery of IRG and Gbp proteins to PVs requires the autophagy factor Atg5. Atg5 is part of a protein complex that facilitates the transfer of the ubiquitin-like protein Atg8 from the E2-like conjugation enzyme Atg3 to the lipid phosphatidylethanolamine. Here, we show that Atg3 expression, similar to Atg5 expression, is required for IRG and Gbp proteins to dock to PVs. We further demonstrate that expression of a dominant-active, GTP-locked IRG protein variant rescues the PV targeting defect of Atg3and Atg5-deficient cells, suggesting a possible role for Atg proteins in the activation of IRG proteins. Lastly, we show that IFN-induced cell-autonomous resistance to C. trachomatis infections in mouse cells depends not only on Atg5 and IRG proteins, as previously demonstrated, but also requires the expression of Atg3 and Gbp proteins. These findings provide a foundation for a better understanding of IRG-and Gbp-dependent cell-autonomous resistance and its regulation by Atg proteins.","publication_date":{"day":null,"month":null,"year":2014,"errors":{}},"publication_name":"PLoS ONE","grobid_abstract_attachment_id":73195502},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101113/The_E2_Like_Conjugation_Enzyme_Atg3_Promotes_Binding_of_IRG_and_Gbp_Proteins_to_Chlamydia_and_Toxoplasma_Containing_Vacuoles_and_Host_Resistance","translated_internal_url":"","created_at":"2021-10-20T04:15:54.474-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195502,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195502/thumbnails/1.jpg","file_name":"106d972197e05ab1b51068491caedfb52166.pdf","download_url":"https://www.academia.edu/attachments/73195502/download_file","bulk_download_file_name":"The_E2_Like_Conjugation_Enzyme_Atg3_Prom.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195502/106d972197e05ab1b51068491caedfb52166-libre.pdf?1634732281=\u0026response-content-disposition=attachment%3B+filename%3DThe_E2_Like_Conjugation_Enzyme_Atg3_Prom.pdf\u0026Expires=1743659393\u0026Signature=TPLF8COA24-ynQfk0qFagE6-CwZFJLCaoLqgibX3pKYDPa1EAFrsQRWra7cS79BQcROnc0BG0tBvkiyztcgY2JjH0ykBKwBxM8WrdREpBkZNvOi8g8sAQqfghGQikMw0AWBRJajYFj8JxAE9Lx0IpfvWi4ZnLmZqWsy4QvZog5Ej7rhT8DBlMw9KVpQ5HKWN~jgL26glqRoCL5BHVWaIXZrRaBRrY8YS9NJFu~ZCjxEU8zMIx4LiQhvVAwEishdAdktvZvFrq07x-wF1UMAnCa12mQWBAPy63b3Co7RrnahGY-g1JoJwAIqSchzHV3IxRLRjbuyqTfDRb6sULjCw0Q__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"The_E2_Like_Conjugation_Enzyme_Atg3_Promotes_Binding_of_IRG_and_Gbp_Proteins_to_Chlamydia_and_Toxoplasma_Containing_Vacuoles_and_Host_Resistance","translated_slug":"","page_count":9,"language":"en","content_type":"Work","summary":"Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathogen Toxoplasma gondii is controlled by two families of Interferon (IFN)-inducible GTPases: Immunity Related GTPases (IRGs) and Guanylate binding proteins (Gbps). Members of these two GTPase families associate with pathogen-containing vacuoles (PVs) and solicit antimicrobial resistance pathways specifically to the intracellular site of infection. The proper delivery of IRG and Gbp proteins to PVs requires the autophagy factor Atg5. Atg5 is part of a protein complex that facilitates the transfer of the ubiquitin-like protein Atg8 from the E2-like conjugation enzyme Atg3 to the lipid phosphatidylethanolamine. Here, we show that Atg3 expression, similar to Atg5 expression, is required for IRG and Gbp proteins to dock to PVs. We further demonstrate that expression of a dominant-active, GTP-locked IRG protein variant rescues the PV targeting defect of Atg3and Atg5-deficient cells, suggesting a possible role for Atg proteins in the activation of IRG proteins. Lastly, we show that IFN-induced cell-autonomous resistance to C. trachomatis infections in mouse cells depends not only on Atg5 and IRG proteins, as previously demonstrated, but also requires the expression of Atg3 and Gbp proteins. These findings provide a foundation for a better understanding of IRG-and Gbp-dependent cell-autonomous resistance and its regulation by Atg proteins.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195502,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195502/thumbnails/1.jpg","file_name":"106d972197e05ab1b51068491caedfb52166.pdf","download_url":"https://www.academia.edu/attachments/73195502/download_file","bulk_download_file_name":"The_E2_Like_Conjugation_Enzyme_Atg3_Prom.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195502/106d972197e05ab1b51068491caedfb52166-libre.pdf?1634732281=\u0026response-content-disposition=attachment%3B+filename%3DThe_E2_Like_Conjugation_Enzyme_Atg3_Prom.pdf\u0026Expires=1743659393\u0026Signature=TPLF8COA24-ynQfk0qFagE6-CwZFJLCaoLqgibX3pKYDPa1EAFrsQRWra7cS79BQcROnc0BG0tBvkiyztcgY2JjH0ykBKwBxM8WrdREpBkZNvOi8g8sAQqfghGQikMw0AWBRJajYFj8JxAE9Lx0IpfvWi4ZnLmZqWsy4QvZog5Ej7rhT8DBlMw9KVpQ5HKWN~jgL26glqRoCL5BHVWaIXZrRaBRrY8YS9NJFu~ZCjxEU8zMIx4LiQhvVAwEishdAdktvZvFrq07x-wF1UMAnCa12mQWBAPy63b3Co7RrnahGY-g1JoJwAIqSchzHV3IxRLRjbuyqTfDRb6sULjCw0Q__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":48,"name":"Engineering","url":"https://www.academia.edu/Documents/in/Engineering"},{"id":498,"name":"Physics","url":"https://www.academia.edu/Documents/in/Physics"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":13346,"name":"Toxoplasma","url":"https://www.academia.edu/Documents/in/Toxoplasma"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":34106,"name":"Chlamydia trachomatis","url":"https://www.academia.edu/Documents/in/Chlamydia_trachomatis"},{"id":37798,"name":"Toxoplasmosis","url":"https://www.academia.edu/Documents/in/Toxoplasmosis"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":84924,"name":"Immunity","url":"https://www.academia.edu/Documents/in/Immunity"},{"id":105062,"name":"Disease resistance","url":"https://www.academia.edu/Documents/in/Disease_resistance"},{"id":220780,"name":"PLoS one","url":"https://www.academia.edu/Documents/in/PLoS_one"},{"id":284067,"name":"Inclusion Bodies","url":"https://www.academia.edu/Documents/in/Inclusion_Bodies"},{"id":418954,"name":"Guanosine Triphosphate","url":"https://www.academia.edu/Documents/in/Guanosine_Triphosphate"},{"id":1010725,"name":"Protein Binding","url":"https://www.academia.edu/Documents/in/Protein_Binding"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":2428330,"name":"Vacuoles","url":"https://www.academia.edu/Documents/in/Vacuoles"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101113-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="53277781"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/53277781/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins"><img alt="Research paper thumbnail of IRG and GBP Host Resistance Factors Target Aberrant, ''Non-self'' Vacuoles Characterized by the Missing of ''Self'' IRGM Proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/70189962/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/53277781/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins">IRG and GBP Host Resistance Factors Target Aberrant, ''Non-self'' Vacuoles Characterized by the Missing of ''Self'' IRGM Proteins</a></div><div class="wp-workCard_item"><span>PLoS Pathogens</span><span>, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with ''non-self'' PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on ''self'' organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="be16f4608b659b364a04e655cd9259c8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":70189962,"asset_id":53277781,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/70189962/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="53277781"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="53277781"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 53277781; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=53277781]").text(description); $(".js-view-count[data-work-id=53277781]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 53277781; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='53277781']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "be16f4608b659b364a04e655cd9259c8" } } $('.js-work-strip[data-work-id=53277781]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":53277781,"title":"IRG and GBP Host Resistance Factors Target Aberrant, ''Non-self'' Vacuoles Characterized by the Missing of ''Self'' IRGM Proteins","translated_title":"","metadata":{"abstract":"Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. 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These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.","publication_date":{"day":null,"month":null,"year":2013,"errors":{}},"publication_name":"PLoS Pathogens"},"translated_abstract":"Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. 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These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":70189962,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/70189962/thumbnails/1.jpg","file_name":"AK_HALDAR_PLoS_Pathogens_2013.pdf","download_url":"https://www.academia.edu/attachments/70189962/download_file","bulk_download_file_name":"IRG_and_GBP_Host_Resistance_Factors_Targ.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/70189962/AK_HALDAR_PLoS_Pathogens_2013-libre.pdf?1632464632=\u0026response-content-disposition=attachment%3B+filename%3DIRG_and_GBP_Host_Resistance_Factors_Targ.pdf\u0026Expires=1743659393\u0026Signature=H4YxTw-YU94n2Xlu5qnps945MU2BLv6vaKWBy6FMc7S8YYk5nINDlXAHpkh500XlRUDiwzmqooEkOsIZmQhSdcHkeqINY0yfHNqj82L76KVeCXDPZ9jHU6k1FcSiiXLILh47yzPreqHhRjmr9-dtG8k5SM2MKj81~pQqefGrnbdiG3qUzKMjmMOZ6or9dNxxaZN5uF3vqRVQlx9kKrD4rYA88IZKyqoTd8gOwFRf2RYov6aM47oPU~vLe8gwDy9RbnCq~GACY7VhTax7FNQjqmEA8J474p0lrwe4se86Rq8FSXreGLU-7vtbY~yVEI3yda3816pBJChYLx1lPQrDxA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-53277781-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="53198778"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/53198778/Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_%CE%B3_to_IL_10_ratio"><img alt="Research paper thumbnail of Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio" class="work-thumbnail" src="https://attachments.academia-assets.com/70099751/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/53198778/Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_%CE%B3_to_IL_10_ratio">Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio</a></div><div class="wp-workCard_item"><span>Experimental Parasitology</span><span>, 2009</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and t...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O2)2(H2O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (SbR) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-γ and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-γ inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="3245a5697c3cb876056b8d44312b8030" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":70099751,"asset_id":53198778,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/70099751/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="53198778"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="53198778"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 53198778; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=53198778]").text(description); $(".js-view-count[data-work-id=53198778]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 53198778; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='53198778']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "3245a5697c3cb876056b8d44312b8030" } } $('.js-work-strip[data-work-id=53198778]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":53198778,"title":"Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio","translated_title":"","metadata":{"abstract":"We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O2)2(H2O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (SbR) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-γ and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-γ inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.","publication_date":{"day":null,"month":null,"year":2009,"errors":{}},"publication_name":"Experimental Parasitology"},"translated_abstract":"We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O2)2(H2O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (SbR) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-γ and concomitant decrease in IL-10 production. 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Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.","internal_url":"https://www.academia.edu/53198778/Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_%CE%B3_to_IL_10_ratio","translated_internal_url":"","created_at":"2021-09-22T00:38:11.732-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":36898670,"work_id":53198778,"tagging_user_id":144833746,"tagged_user_id":null,"co_author_invite_id":7305610,"email":"b***a@gmail.com","display_order":1,"name":"Subha Banerjee","title":"Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio"},{"id":36898671,"work_id":53198778,"tagging_user_id":144833746,"tagged_user_id":null,"co_author_invite_id":7305611,"email":"k***8@gmail.com","display_order":2,"name":"Kshudiram Naskar","title":"Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio"},{"id":36898672,"work_id":53198778,"tagging_user_id":144833746,"tagged_user_id":null,"co_author_invite_id":7305612,"email":"d***k@rediffmail.com","display_order":3,"name":"Diganta Kalita","title":"Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio"},{"id":36898673,"work_id":53198778,"tagging_user_id":144833746,"tagged_user_id":null,"co_author_invite_id":98347,"email":"s***y@iicb.res.in","display_order":4,"name":"Syamal Roy","title":"Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio"}],"downloadable_attachments":[{"id":70099751,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/70099751/thumbnails/1.jpg","file_name":"r_AK_HALDAR_Experimental_Parasitology_2009.pdf","download_url":"https://www.academia.edu/attachments/70099751/download_file","bulk_download_file_name":"Sub_optimal_dose_of_Sodium_Antimony_Gluc.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/70099751/r_AK_HALDAR_Experimental_Parasitology_2009-libre.pdf?1632298597=\u0026response-content-disposition=attachment%3B+filename%3DSub_optimal_dose_of_Sodium_Antimony_Gluc.pdf\u0026Expires=1743659393\u0026Signature=X15oawJC9qriwvaFl3Vtz07wrGKvrJZeKTAaDoUXRmPGJLNQXoX7vwEmmreG9TpnD3FcliRc4IyyQuWf87g~a6qvuqC-z3vyu74xaLkKv37y~kvBrKcLKevkgzSZ7Q8ORF6L4ZMAUp6oQuVh1cKC5zoSMu78lALnZSFcL1KHhQgiuN5BUS-AN80HtdmS~iXrNLDO7TFEg0JJbxKqTzFR-nLw~H00ndcNnfJY2buEqhfmpcM3aXTXKj3PX2DdKdaj~9oL9dkBR~6YaPqS~5sTCqzIjq9znuvmuMPLREN0yU78OE2WNljNt41jkvvmWsGsrDKC9utjLcifKtcl5x2qHg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_γ_to_IL_10_ratio","translated_slug":"","page_count":11,"language":"en","content_type":"Work","summary":"We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O2)2(H2O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (SbR) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-γ and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-γ inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. 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For instance, members of the GBP family translocate to PVs occupied by the protozoan pathogen Toxoplasma and facilitate PV disruption and lytic parasite killing. While the GBP defense program targeting Toxoplasma has been studied in some detail, the role of GBPs in host defense to other protozoan pathogens is poorly characterized. Here, we report a critical role for both mouse and human GBPs in the cell-autonomous immune response against the vector-borne parasite Leishmania donovani. Although L. donovani can infect both phagocytic and nonphagocytic cells, it predominantly replicates inside professional phagocytes. The underlying basis for this cell type tropism is unclear. Here, we demonstrate that GBPs restrict growth of L. donovani in both mouse and human nonphagocytic cells. GBP-mediated restr...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="76ece5a756f7703da230aa9c87061b6a" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":82585654,"asset_id":74428355,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/82585654/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="74428355"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="74428355"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 74428355; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=74428355]").text(description); $(".js-view-count[data-work-id=74428355]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 74428355; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='74428355']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "76ece5a756f7703da230aa9c87061b6a" } } $('.js-work-strip[data-work-id=74428355]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":74428355,"title":"Guanylate Binding Proteins Restrict Leishmania donovani Growth in Nonphagocytic Cells Independent of Parasitophorous Vacuolar Targeting","translated_title":"","metadata":{"abstract":"Interferon (IFN)-inducible guanylate binding proteins (GBPs) play important roles in host defense against many intracellular pathogens that reside within pathogen-containing vacuoles (PVs). For instance, members of the GBP family translocate to PVs occupied by the protozoan pathogen Toxoplasma and facilitate PV disruption and lytic parasite killing. While the GBP defense program targeting Toxoplasma has been studied in some detail, the role of GBPs in host defense to other protozoan pathogens is poorly characterized. Here, we report a critical role for both mouse and human GBPs in the cell-autonomous immune response against the vector-borne parasite Leishmania donovani. Although L. donovani can infect both phagocytic and nonphagocytic cells, it predominantly replicates inside professional phagocytes. The underlying basis for this cell type tropism is unclear. Here, we demonstrate that GBPs restrict growth of L. donovani in both mouse and human nonphagocytic cells. GBP-mediated restr...","publisher":"American Society for Microbiology","publication_name":"mBio"},"translated_abstract":"Interferon (IFN)-inducible guanylate binding proteins (GBPs) play important roles in host defense against many intracellular pathogens that reside within pathogen-containing vacuoles (PVs). For instance, members of the GBP family translocate to PVs occupied by the protozoan pathogen Toxoplasma and facilitate PV disruption and lytic parasite killing. While the GBP defense program targeting Toxoplasma has been studied in some detail, the role of GBPs in host defense to other protozoan pathogens is poorly characterized. Here, we report a critical role for both mouse and human GBPs in the cell-autonomous immune response against the vector-borne parasite Leishmania donovani. Although L. donovani can infect both phagocytic and nonphagocytic cells, it predominantly replicates inside professional phagocytes. The underlying basis for this cell type tropism is unclear. Here, we demonstrate that GBPs restrict growth of L. donovani in both mouse and human nonphagocytic cells. GBP-mediated restr...","internal_url":"https://www.academia.edu/74428355/Guanylate_Binding_Proteins_Restrict_Leishmania_donovani_Growth_in_Nonphagocytic_Cells_Independent_of_Parasitophorous_Vacuolar_Targeting","translated_internal_url":"","created_at":"2022-03-23T22:34:53.075-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":82585654,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/82585654/thumbnails/1.jpg","file_name":"e01464-20.full.pdf","download_url":"https://www.academia.edu/attachments/82585654/download_file","bulk_download_file_name":"Guanylate_Binding_Proteins_Restrict_Leis.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/82585654/e01464-20.full-libre.pdf?1648104641=\u0026response-content-disposition=attachment%3B+filename%3DGuanylate_Binding_Proteins_Restrict_Leis.pdf\u0026Expires=1743659392\u0026Signature=U4EjDHJ0XFv3LW33VdURHZClLubner2PWTxf28FTk3g~OEc3QgfSZq3ejFUOH4yjPhk7U-8M3hfohAsz2p6qNuFdNSC-ZsMFhkW10JZgursMRIBi51rdWwMhTcPFqoRTtWcnbbu-0NtfIAfAdNqIsIdDRd6JX7nEQIr2UKLJrJJi8sYtiLBydiu3WL~17~tP9puPUM0zCypuyZKPQV5jmm43Fg~vd0f95tzAedbOMbpKwZc5tU1INIIvHRP6MS12IYervT-AaZWncXMwxFWKjcZ1knQn0lL3oAv1IYCXU2Da7uFjqiiLMF0Umt~vmb~rsj10FYUu7ERyNJM3fudxiQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Guanylate_Binding_Proteins_Restrict_Leishmania_donovani_Growth_in_Nonphagocytic_Cells_Independent_of_Parasitophorous_Vacuolar_Targeting","translated_slug":"","page_count":19,"language":"en","content_type":"Work","summary":"Interferon (IFN)-inducible guanylate binding proteins (GBPs) play important roles in host defense against many intracellular pathogens that reside within pathogen-containing vacuoles (PVs). For instance, members of the GBP family translocate to PVs occupied by the protozoan pathogen Toxoplasma and facilitate PV disruption and lytic parasite killing. While the GBP defense program targeting Toxoplasma has been studied in some detail, the role of GBPs in host defense to other protozoan pathogens is poorly characterized. Here, we report a critical role for both mouse and human GBPs in the cell-autonomous immune response against the vector-borne parasite Leishmania donovani. Although L. donovani can infect both phagocytic and nonphagocytic cells, it predominantly replicates inside professional phagocytes. The underlying basis for this cell type tropism is unclear. Here, we demonstrate that GBPs restrict growth of L. donovani in both mouse and human nonphagocytic cells. GBP-mediated restr...","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":82585654,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/82585654/thumbnails/1.jpg","file_name":"e01464-20.full.pdf","download_url":"https://www.academia.edu/attachments/82585654/download_file","bulk_download_file_name":"Guanylate_Binding_Proteins_Restrict_Leis.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/82585654/e01464-20.full-libre.pdf?1648104641=\u0026response-content-disposition=attachment%3B+filename%3DGuanylate_Binding_Proteins_Restrict_Leis.pdf\u0026Expires=1743659392\u0026Signature=U4EjDHJ0XFv3LW33VdURHZClLubner2PWTxf28FTk3g~OEc3QgfSZq3ejFUOH4yjPhk7U-8M3hfohAsz2p6qNuFdNSC-ZsMFhkW10JZgursMRIBi51rdWwMhTcPFqoRTtWcnbbu-0NtfIAfAdNqIsIdDRd6JX7nEQIr2UKLJrJJi8sYtiLBydiu3WL~17~tP9puPUM0zCypuyZKPQV5jmm43Fg~vd0f95tzAedbOMbpKwZc5tU1INIIvHRP6MS12IYervT-AaZWncXMwxFWKjcZ1knQn0lL3oAv1IYCXU2Da7uFjqiiLMF0Umt~vmb~rsj10FYUu7ERyNJM3fudxiQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":874509,"name":"Mbio","url":"https://www.academia.edu/Documents/in/Mbio"}],"urls":[{"id":18750248,"url":"https://syndication.highwire.org/content/doi/10.1128/mBio.01464-20"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-74428355-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="63301730"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/63301730/Dynamin_related_Irgm_proteins_modulate_LPS_induced_caspase_4_activation_and_septic_shock"><img alt="Research paper thumbnail of Dynamin-related Irgm proteins modulate LPS-induced caspase-4 activation and septic shock" class="work-thumbnail" src="https://attachments.academia-assets.com/75776656/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/63301730/Dynamin_related_Irgm_proteins_modulate_LPS_induced_caspase_4_activation_and_septic_shock">Dynamin-related Irgm proteins modulate LPS-induced caspase-4 activation and septic shock</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Inflammation associated with gram-negative bacterial infections is often instigated by the bacter...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Inflammation associated with gram-negative bacterial infections is often instigated by the bacterial cell wall component lipopolysaccharide (LPS). LPS-induced inflammation and resulting life-threatening sepsis are mediated by the two distinct LPS receptors TLR4 and caspase-4. Whereas the regulation of TLR4 activation by extracellular and phago-endosomal LPS has been studied in great detail, auxiliary host factors that specifically modulate recognition of cytosolic LPS by caspase-4 are largely unknown. This study identifies dynamin-related membrane remodeling proteins belonging to the family of Immunity related GTPases M clade (IRGM) as negative regulators of caspase-4 activation in macrophages. Phagocytes lacking expression of mouse isoform Irgm2 aberrantly activate caspase-4-dependent inflammatory responses when exposed to extracellular LPS, bacterial outer membrane vesicles or gram-negative bacteria. Consequently, Irgm2-deficient mice display increased susceptibility to caspase-4mediated septic shock in vivo. This Irgm2 phenotype is partly reversed by the simultaneous genetic deletion of the two additional Irgm paralogs Irgm1 and Irgm3, indicating that dysregulated Irgm isoform expression disrupts intracellular LPS processing pathways that limit LPS availability for caspase-4 activation.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b94ee82ff040ae778c16d4dc7f61cdc1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":75776656,"asset_id":63301730,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/75776656/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="63301730"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="63301730"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 63301730; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=63301730]").text(description); $(".js-view-count[data-work-id=63301730]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 63301730; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='63301730']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b94ee82ff040ae778c16d4dc7f61cdc1" } } $('.js-work-strip[data-work-id=63301730]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":63301730,"title":"Dynamin-related Irgm proteins modulate LPS-induced caspase-4 activation and septic shock","translated_title":"","metadata":{"publisher":"Cold Spring Harbor Laboratory","grobid_abstract":"Inflammation associated with gram-negative bacterial infections is often instigated by the bacterial cell wall component lipopolysaccharide (LPS). 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This Irgm2 phenotype is partly reversed by the simultaneous genetic deletion of the two additional Irgm paralogs Irgm1 and Irgm3, indicating that dysregulated Irgm isoform expression disrupts intracellular LPS processing pathways that limit LPS availability for caspase-4 activation.","publication_date":{"day":20,"month":3,"year":2020,"errors":{}},"grobid_abstract_attachment_id":75776656},"translated_abstract":null,"internal_url":"https://www.academia.edu/63301730/Dynamin_related_Irgm_proteins_modulate_LPS_induced_caspase_4_activation_and_septic_shock","translated_internal_url":"","created_at":"2021-12-05T22:57:26.033-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":75776656,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/75776656/thumbnails/1.jpg","file_name":"2020.03.18.997460.full.pdf","download_url":"https://www.academia.edu/attachments/75776656/download_file","bulk_download_file_name":"Dynamin_related_Irgm_proteins_modulate_L.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/75776656/2020.03.18.997460.full-libre.pdf?1638780272=\u0026response-content-disposition=attachment%3B+filename%3DDynamin_related_Irgm_proteins_modulate_L.pdf\u0026Expires=1743659392\u0026Signature=APukkRib26Yzai05-WrlUnsS2F5mgLNkluwE3HIHQW3kXMF9vzdPl8JnuQRV-jizFc50FiMI2n7PC7xZDnFTLMqM8F6oGwQ57ACGTzMGcHZcBTdwjq0R7VX9ImORI4MQrc3p-tyoVtc3lvIDigHgUekYjBtYgTMKm7d-uYv961m5C5fU4gYsCkMiqTcEYzOhHhSoK-2tSO-M78xiiUDtffxz-3atG4986CXFEBNk4EQlVX0PKogl7-sMyoMtOZ1pU4XJoS1RAudXMBIgYiyni5USXJ6myj0fzMdgB7FIup0uo3ZEIcgkTjqs90b9YV4kp~B-ZYY8fv~Me6BVHUDzhA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Dynamin_related_Irgm_proteins_modulate_LPS_induced_caspase_4_activation_and_septic_shock","translated_slug":"","page_count":70,"language":"en","content_type":"Work","summary":"Inflammation associated with gram-negative bacterial infections is often instigated by the bacterial cell wall component lipopolysaccharide (LPS). 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Host guanylate binding proteins (GBPs) promote infection-induced caspase-11 activation in tissue culture models, and yet their in vivo role in LPS-mediated sepsis has remained unexplored. LPS can be released from lysed bacteria as &quot;free&quot; LPS aggregates or actively secreted by live bacteria as a component of outer membrane vesicles (OMVs). Here, we report that GBPs control inflammation and sepsis in mice injected with either free LPS or purified OMVs derived from Gram-negative Escherichia coli In agreement with our observations from in vivo experiments, we demonstrate that macrophages lacking GBP2 expression fail to induce pyroptotic cell death and proinflammatory interleukin-1β (IL-1β) and IL-18 secretion when exposed to OMVs. 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It highlights how IFNg activates host cell mechanisms that lead to the attachment of polyubiquitin chains to these vacuoles, marking them for destruction. The research indicates that while murine cells utilize Immunity Related GTPases (IRGs) for this process, the mechanisms in human cells remain less understood and likely differ from the murine pathway. Ubiquitination appears essential for cell-autonomous immunity to these pathogens and involves multiple E3 ligases, suggesting a complex interaction in evoking immune responses.","publication_date":{"day":null,"month":null,"year":2015,"errors":{}},"publication_name":"Communicative \u0026 Integrative Biology"},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101350/Ubiquitination_of_pathogen_containing_vacuoles_promotes_host_defense_toChlamydia_trachomatisandToxoplasma_gondii","translated_internal_url":"","created_at":"2021-10-20T04:19:29.489-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195675,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195675/thumbnails/1.jpg","file_name":"pmc4802790.pdf","download_url":"https://www.academia.edu/attachments/73195675/download_file","bulk_download_file_name":"Ubiquitination_of_pathogen_containing_va.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195675/pmc4802790-libre.pdf?1634732266=\u0026response-content-disposition=attachment%3B+filename%3DUbiquitination_of_pathogen_containing_va.pdf\u0026Expires=1743659392\u0026Signature=R7Ns75Nqr0GRl~AxqyMui97dQWN5izMFWn5-kXhGWbFrjRdUc7LOJ7SPtITVoQ0vj6yQaBOPmauEUnaQAav38j2MifS~cVRzcPFNccMwDgDdPO66t0v8fhMNUsfkb6W4HPaAfXNw5zhE83IQSRoQ7VgtGVxHyZks0J7YQ-kpSeuIYckCr2M8Vlxk-bmMnsUB5t5fLT-~bssDzu0ZEqEmCtyBphPqAoxM21YIBClTUIHJ-339bik07dyAMuKpf-vWD3OeRpi2Z99tObi7k3VTHw4D3pLefCJVC~xshwicamFDRdQeKbqV-YuNOg~CQ6d6TwqW3uf4jL6JzcWom3n-Tw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Ubiquitination_of_pathogen_containing_vacuoles_promotes_host_defense_toChlamydia_trachomatisandToxoplasma_gondii","translated_slug":"","page_count":3,"language":"en","content_type":"Work","summary":null,"owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195675,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195675/thumbnails/1.jpg","file_name":"pmc4802790.pdf","download_url":"https://www.academia.edu/attachments/73195675/download_file","bulk_download_file_name":"Ubiquitination_of_pathogen_containing_va.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195675/pmc4802790-libre.pdf?1634732266=\u0026response-content-disposition=attachment%3B+filename%3DUbiquitination_of_pathogen_containing_va.pdf\u0026Expires=1743659392\u0026Signature=R7Ns75Nqr0GRl~AxqyMui97dQWN5izMFWn5-kXhGWbFrjRdUc7LOJ7SPtITVoQ0vj6yQaBOPmauEUnaQAav38j2MifS~cVRzcPFNccMwDgDdPO66t0v8fhMNUsfkb6W4HPaAfXNw5zhE83IQSRoQ7VgtGVxHyZks0J7YQ-kpSeuIYckCr2M8Vlxk-bmMnsUB5t5fLT-~bssDzu0ZEqEmCtyBphPqAoxM21YIBClTUIHJ-339bik07dyAMuKpf-vWD3OeRpi2Z99tObi7k3VTHw4D3pLefCJVC~xshwicamFDRdQeKbqV-YuNOg~CQ6d6TwqW3uf4jL6JzcWom3n-Tw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101350-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101346"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101346/Ubiquitin_systems_mark_pathogen_containing_vacuoles_as_targets_for_host_defense_by_guanylate_binding_proteins"><img alt="Research paper thumbnail of Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/73195672/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101346/Ubiquitin_systems_mark_pathogen_containing_vacuoles_as_targets_for_host_defense_by_guanylate_binding_proteins">Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins</a></div><div class="wp-workCard_item"><span>Proceedings of the National Academy of Sciences</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche pe...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f2eb507af94090838c9674d63848711c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195672,"asset_id":59101346,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195672/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101346"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101346"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101346; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101346]").text(description); $(".js-view-count[data-work-id=59101346]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101346; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101346']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "f2eb507af94090838c9674d63848711c" } } $('.js-work-strip[data-work-id=59101346]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101346,"title":"Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins","translated_title":"","metadata":{"abstract":"Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage ...","publisher":"Proceedings of the National Academy of Sciences","ai_title_tag":"Ubiquitin marks pathogen vacuoles for GBP-mediated immunity","publication_date":{"day":null,"month":null,"year":2015,"errors":{}},"publication_name":"Proceedings of the National Academy of Sciences"},"translated_abstract":"Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage ...","internal_url":"https://www.academia.edu/59101346/Ubiquitin_systems_mark_pathogen_containing_vacuoles_as_targets_for_host_defense_by_guanylate_binding_proteins","translated_internal_url":"","created_at":"2021-10-20T04:19:29.305-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195672,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195672/thumbnails/1.jpg","file_name":"E5628.full.pdf","download_url":"https://www.academia.edu/attachments/73195672/download_file","bulk_download_file_name":"Ubiquitin_systems_mark_pathogen_containi.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195672/E5628.full-libre.pdf?1634732270=\u0026response-content-disposition=attachment%3B+filename%3DUbiquitin_systems_mark_pathogen_containi.pdf\u0026Expires=1743659392\u0026Signature=EUQ3ySBQDyqhgq0AB3M5F-Impv76IjAbloi3F17LKq71NuDzEVIkYgw8ZOm7feMzlzdku31gXt~AnoxJty6y3yE1i0ljTa9uAQ9AYV04yYkYFqtQXXEEjylU-2Oh8VY0ckzU-jJWItNn6yN9qOCJCIlYbMI-7BHQgYQek6b0wWYezTie5RbiLH~idYpuZ73X~RFM44TJ3hUygQM9grGy-quVhiNjzNTAEVIkiIw2EP8vsaSI2NPoND4UYZ-zwaTeA21iMBn8DUArTe8OXzddfa5ZA~9jOKkFy-uJDpWUiobRgoXWX~dBjD~FfA9kQ5qAQ-HeKyyoonVyfUkr2d0slA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Ubiquitin_systems_mark_pathogen_containing_vacuoles_as_targets_for_host_defense_by_guanylate_binding_proteins","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage ...","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195672,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195672/thumbnails/1.jpg","file_name":"E5628.full.pdf","download_url":"https://www.academia.edu/attachments/73195672/download_file","bulk_download_file_name":"Ubiquitin_systems_mark_pathogen_containi.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195672/E5628.full-libre.pdf?1634732270=\u0026response-content-disposition=attachment%3B+filename%3DUbiquitin_systems_mark_pathogen_containi.pdf\u0026Expires=1743659392\u0026Signature=EUQ3ySBQDyqhgq0AB3M5F-Impv76IjAbloi3F17LKq71NuDzEVIkYgw8ZOm7feMzlzdku31gXt~AnoxJty6y3yE1i0ljTa9uAQ9AYV04yYkYFqtQXXEEjylU-2Oh8VY0ckzU-jJWItNn6yN9qOCJCIlYbMI-7BHQgYQek6b0wWYezTie5RbiLH~idYpuZ73X~RFM44TJ3hUygQM9grGy-quVhiNjzNTAEVIkiIw2EP8vsaSI2NPoND4UYZ-zwaTeA21iMBn8DUArTe8OXzddfa5ZA~9jOKkFy-uJDpWUiobRgoXWX~dBjD~FfA9kQ5qAQ-HeKyyoonVyfUkr2d0slA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":13346,"name":"Toxoplasma","url":"https://www.academia.edu/Documents/in/Toxoplasma"},{"id":24706,"name":"Innate immunity","url":"https://www.academia.edu/Documents/in/Innate_immunity"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":34106,"name":"Chlamydia trachomatis","url":"https://www.academia.edu/Documents/in/Chlamydia_trachomatis"},{"id":37798,"name":"Toxoplasmosis","url":"https://www.academia.edu/Documents/in/Toxoplasmosis"},{"id":55266,"name":"Ubiquitin","url":"https://www.academia.edu/Documents/in/Ubiquitin"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":143257,"name":"PNAS","url":"https://www.academia.edu/Documents/in/PNAS"},{"id":279576,"name":"Immune Evasion","url":"https://www.academia.edu/Documents/in/Immune_Evasion"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":2428330,"name":"Vacuoles","url":"https://www.academia.edu/Documents/in/Vacuoles"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101346-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101343"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101343/Guanylate_Binding_Proteins_enable_rapid_activation_of_canonical_and_noncanonical_inflammasomes_in_Chlamydia_infected_macrophages"><img alt="Research paper thumbnail of Guanylate Binding Proteins enable rapid activation of canonical and noncanonical inflammasomes in Chlamydia-infected macrophages" class="work-thumbnail" src="https://attachments.academia-assets.com/73195665/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101343/Guanylate_Binding_Proteins_enable_rapid_activation_of_canonical_and_noncanonical_inflammasomes_in_Chlamydia_infected_macrophages">Guanylate Binding Proteins enable rapid activation of canonical and noncanonical inflammasomes in Chlamydia-infected macrophages</a></div><div class="wp-workCard_item"><span>Infection and immunity</span><span>, Jan 28, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Interferon (IFN)-inducible Guanylate Binding Proteins (GBPs) mediate cell-autonomous host resista...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Interferon (IFN)-inducible Guanylate Binding Proteins (GBPs) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. The prevailing model postulates that these two GBP-controlled activities are directly linked through GBP-dependent vacuolar lysis. It was proposed that rupture of pathogen-containing vacuoles (PVs) by GBPs destroyed the microbial refuge and simultaneously contaminated the host cell cytosol with microbial activators of inflammasomes. Here, we demonstrate that GBP-mediated host resistance and GBP-mediated inflammatory responses can be uncoupled. We show that PVs formed by the rodent pathogen Chlamydia muridarum, so-called inclusions, remain free of GBPs and that C. muridarum is impervious to GBP-mediated restrictions on bacterial growth. Although GBPs neither bind to C. muridarum inclusions nor restrict C. muridarum growth, we find that GBPs promote inflammasome activation in C. muridarum-infected macrophages. We demonstrate t...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="74dfffa3e02436a8ff8d919521d3c70c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195665,"asset_id":59101343,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195665/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101343"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101343"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101343; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101343]").text(description); $(".js-view-count[data-work-id=59101343]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101343; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101343']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "74dfffa3e02436a8ff8d919521d3c70c" } } $('.js-work-strip[data-work-id=59101343]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101343,"title":"Guanylate Binding Proteins enable rapid activation of canonical and noncanonical inflammasomes in Chlamydia-infected macrophages","translated_title":"","metadata":{"abstract":"Interferon (IFN)-inducible Guanylate Binding Proteins (GBPs) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. The prevailing model postulates that these two GBP-controlled activities are directly linked through GBP-dependent vacuolar lysis. It was proposed that rupture of pathogen-containing vacuoles (PVs) by GBPs destroyed the microbial refuge and simultaneously contaminated the host cell cytosol with microbial activators of inflammasomes. Here, we demonstrate that GBP-mediated host resistance and GBP-mediated inflammatory responses can be uncoupled. We show that PVs formed by the rodent pathogen Chlamydia muridarum, so-called inclusions, remain free of GBPs and that C. muridarum is impervious to GBP-mediated restrictions on bacterial growth. Although GBPs neither bind to C. muridarum inclusions nor restrict C. muridarum growth, we find that GBPs promote inflammasome activation in C. muridarum-infected macrophages. We demonstrate t...","publication_date":{"day":28,"month":1,"year":2015,"errors":{}},"publication_name":"Infection and immunity"},"translated_abstract":"Interferon (IFN)-inducible Guanylate Binding Proteins (GBPs) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. The prevailing model postulates that these two GBP-controlled activities are directly linked through GBP-dependent vacuolar lysis. It was proposed that rupture of pathogen-containing vacuoles (PVs) by GBPs destroyed the microbial refuge and simultaneously contaminated the host cell cytosol with microbial activators of inflammasomes. Here, we demonstrate that GBP-mediated host resistance and GBP-mediated inflammatory responses can be uncoupled. We show that PVs formed by the rodent pathogen Chlamydia muridarum, so-called inclusions, remain free of GBPs and that C. muridarum is impervious to GBP-mediated restrictions on bacterial growth. Although GBPs neither bind to C. muridarum inclusions nor restrict C. muridarum growth, we find that GBPs promote inflammasome activation in C. muridarum-infected macrophages. 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We demonstrate t...","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195665,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195665/thumbnails/1.jpg","file_name":"4740.full.pdf","download_url":"https://www.academia.edu/attachments/73195665/download_file","bulk_download_file_name":"Guanylate_Binding_Proteins_enable_rapid.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195665/4740.full-libre.pdf?1634732272=\u0026response-content-disposition=attachment%3B+filename%3DGuanylate_Binding_Proteins_enable_rapid.pdf\u0026Expires=1743659393\u0026Signature=fGc6BHytyUNPsXf2KftVs-neHfjNDjy-9-Vej~1PAH--WXLamI6nKukCTC1USXJ5WhydxhIHMUlNvpRZs--99KNo8uFKqx8fIi3EDfecs3OFWh~9QWnpvcJ-ABuriL001ArUyoaphbK5eqA2YOI5-Zj5sTbsjBqN~45QQIkUui~QLh8taqmCabEdAVCNBCLj3iZ1XaUNvtWdIXLPSgNk3-~1Xgoz-N6kZl50j7M-vx5ioTeAXpXB~ZEK9jUmHIxpJJhglA6P3rVW4ubDfb~UHPqeq6~NVFWrLK-tjqIDoCbPpqxjwaMIXtVMLx7hVVun3CCDOsZJGrWNKKLu~T6mEg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":34106,"name":"Chlamydia trachomatis","url":"https://www.academia.edu/Documents/in/Chlamydia_trachomatis"},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":48758,"name":"Infection and immunity","url":"https://www.academia.edu/Documents/in/Infection_and_immunity"},{"id":50841,"name":"Caspases","url":"https://www.academia.edu/Documents/in/Caspases"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":284067,"name":"Inclusion Bodies","url":"https://www.academia.edu/Documents/in/Inclusion_Bodies"},{"id":585385,"name":"Primary Cell Culture","url":"https://www.academia.edu/Documents/in/Primary_Cell_Culture"},{"id":743643,"name":"Host Pathogen Interactions","url":"https://www.academia.edu/Documents/in/Host_Pathogen_Interactions"},{"id":886608,"name":"Inflammasomes","url":"https://www.academia.edu/Documents/in/Inflammasomes"},{"id":1186610,"name":"DNA binding proteins","url":"https://www.academia.edu/Documents/in/DNA_binding_proteins"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":1763968,"name":"Gene Expression Regulation","url":"https://www.academia.edu/Documents/in/Gene_Expression_Regulation"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":2428330,"name":"Vacuoles","url":"https://www.academia.edu/Documents/in/Vacuoles"},{"id":2533047,"name":"fibroblasts","url":"https://www.academia.edu/Documents/in/fibroblasts"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101343-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101341"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101341/Use_of_Antimony_in_the_Treatment_of_Leishmaniasis_Current_Status_and_Future_Directions"><img alt="Research paper thumbnail of Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions" class="work-thumbnail" src="https://attachments.academia-assets.com/73195663/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101341/Use_of_Antimony_in_the_Treatment_of_Leishmaniasis_Current_Status_and_Future_Directions">Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions</a></div><div class="wp-workCard_item"><span>Molecular Biology International</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonial...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V)in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistantLeishmania donovaniisolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b92901833db3351d6c3e52ab77f61739" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195663,"asset_id":59101341,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195663/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101341"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101341"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101341; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101341]").text(description); $(".js-view-count[data-work-id=59101341]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101341; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101341']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "b92901833db3351d6c3e52ab77f61739" } } $('.js-work-strip[data-work-id=59101341]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101341,"title":"Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions","translated_title":"","metadata":{"abstract":"In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V)in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistantLeishmania donovaniisolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.","publisher":"Hindawi Limited","ai_title_tag":"Antimony Treatment in Leishmaniasis: Mechanisms and Advances","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Molecular Biology International"},"translated_abstract":"In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V)in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistantLeishmania donovaniisolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.","internal_url":"https://www.academia.edu/59101341/Use_of_Antimony_in_the_Treatment_of_Leishmaniasis_Current_Status_and_Future_Directions","translated_internal_url":"","created_at":"2021-10-20T04:19:29.114-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195663,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195663/thumbnails/1.jpg","file_name":"56c5214eaa5ae3d8169e680f97b6c566e8e0.pdf","download_url":"https://www.academia.edu/attachments/73195663/download_file","bulk_download_file_name":"Use_of_Antimony_in_the_Treatment_of_Leis.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195663/56c5214eaa5ae3d8169e680f97b6c566e8e0-libre.pdf?1634732273=\u0026response-content-disposition=attachment%3B+filename%3DUse_of_Antimony_in_the_Treatment_of_Leis.pdf\u0026Expires=1743659393\u0026Signature=PaKSIiJvyblWV7C35fp-2CK2Ff~RK5M2Ttqgd-pvxKL8ileo95BFu6T4JYlA399d3836Ry3QdNhpdvjridCjuQJJWilhTa37Jgpejuq31nBldqvd9oE0-gTxVM8XIjwCcTbwm0PqkF-vxlSw~x~2EIpZuP3awfORUJyfXK7uysBaO8S69Co0eqtrAe0PPG9FDjWH~k8kL9SUlFvFhRO9rr4VTlVzrpVJ83xJkepp40E38ZD-D-2p~l2Wnty~UkBDNldJAazXMcgkXp3JMtQ6kI9MlFUxmCyYvd9w-O7bNoOaUSc-87l42zLGDAZcee5ADUNmJpQHNjO51l56KEJhiQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Use_of_Antimony_in_the_Treatment_of_Leishmaniasis_Current_Status_and_Future_Directions","translated_slug":"","page_count":23,"language":"en","content_type":"Work","summary":"In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V)in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistantLeishmania donovaniisolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195663,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195663/thumbnails/1.jpg","file_name":"56c5214eaa5ae3d8169e680f97b6c566e8e0.pdf","download_url":"https://www.academia.edu/attachments/73195663/download_file","bulk_download_file_name":"Use_of_Antimony_in_the_Treatment_of_Leis.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195663/56c5214eaa5ae3d8169e680f97b6c566e8e0-libre.pdf?1634732273=\u0026response-content-disposition=attachment%3B+filename%3DUse_of_Antimony_in_the_Treatment_of_Leis.pdf\u0026Expires=1743659393\u0026Signature=PaKSIiJvyblWV7C35fp-2CK2Ff~RK5M2Ttqgd-pvxKL8ileo95BFu6T4JYlA399d3836Ry3QdNhpdvjridCjuQJJWilhTa37Jgpejuq31nBldqvd9oE0-gTxVM8XIjwCcTbwm0PqkF-vxlSw~x~2EIpZuP3awfORUJyfXK7uysBaO8S69Co0eqtrAe0PPG9FDjWH~k8kL9SUlFvFhRO9rr4VTlVzrpVJ83xJkepp40E38ZD-D-2p~l2Wnty~UkBDNldJAazXMcgkXp3JMtQ6kI9MlFUxmCyYvd9w-O7bNoOaUSc-87l42zLGDAZcee5ADUNmJpQHNjO51l56KEJhiQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101341-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101339"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101339/Guanylate_binding_proteins_promote_caspase_11_dependent_pyroptosis_in_response_to_cytoplasmic_LPS"><img alt="Research paper thumbnail of Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS" class="work-thumbnail" src="https://attachments.academia-assets.com/73195686/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101339/Guanylate_binding_proteins_promote_caspase_11_dependent_pyroptosis_in_response_to_cytoplasmic_LPS">Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS</a></div><div class="wp-workCard_item"><span>Proceedings of the National Academy of Sciences</span><span>, 2014</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="39bce8b3558921fe6e7a6a6f5bfd16e4" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195686,"asset_id":59101339,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195686/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101339"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101339"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101339; 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The study highlights that Gbp proteins are crucial for the detection of cytoplasmic LPS in macrophages infected with the respiratory pathogen Legionella pneumophila, ultimately leading to cell-autonomous immunity. Experimental evidence demonstrates that Gbp proteins enhance immune responses to both L. pneumophila and other Gram-negative bacteria like Salmonella and E. coli.","ai_title_tag":"Gbp Proteins Induce Caspase-11 Pyroptosis","publication_date":{"day":null,"month":null,"year":2014,"errors":{}},"publication_name":"Proceedings of the National Academy of Sciences"},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101339/Guanylate_binding_proteins_promote_caspase_11_dependent_pyroptosis_in_response_to_cytoplasmic_LPS","translated_internal_url":"","created_at":"2021-10-20T04:19:29.011-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195686,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195686/thumbnails/1.jpg","file_name":"6046.full.pdf","download_url":"https://www.academia.edu/attachments/73195686/download_file","bulk_download_file_name":"Guanylate_binding_proteins_promote_caspa.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195686/6046.full-libre.pdf?1634732267=\u0026response-content-disposition=attachment%3B+filename%3DGuanylate_binding_proteins_promote_caspa.pdf\u0026Expires=1743659393\u0026Signature=ZcFdRgvEpLfnznYyS8kEP~NBA6Keon~a7KHh3BWY8j-9Sr4PZYFTkGmW~pdRluWX0b59rPFTcRnojATYyPiSn7db06CGhygt3Q4zNgWBLFynjSJxKrdqp8vBGJExxgptRnlzJB83kc0ztWVeBUtjMf3eXVzciBUhHqr9q5qY5pF~VDjKGMRk1nEQlIQD04HSgLeAAsz2DvAGnjZ-pZ2PY4sSQwlldj9Y89gE8BlSdmNdW1APE3mXQMSFjxGRkywPCB4MRxwR-LE9QqKIdBl~SJpskwYROTR~iG0u5Wh9dGsIDqrUzUREHs-CgOxNlwdHJXgvf~ojdE-EWZQetOFcOg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Guanylate_binding_proteins_promote_caspase_11_dependent_pyroptosis_in_response_to_cytoplasmic_LPS","translated_slug":"","page_count":6,"language":"en","content_type":"Work","summary":null,"owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195686,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195686/thumbnails/1.jpg","file_name":"6046.full.pdf","download_url":"https://www.academia.edu/attachments/73195686/download_file","bulk_download_file_name":"Guanylate_binding_proteins_promote_caspa.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195686/6046.full-libre.pdf?1634732267=\u0026response-content-disposition=attachment%3B+filename%3DGuanylate_binding_proteins_promote_caspa.pdf\u0026Expires=1743659393\u0026Signature=ZcFdRgvEpLfnznYyS8kEP~NBA6Keon~a7KHh3BWY8j-9Sr4PZYFTkGmW~pdRluWX0b59rPFTcRnojATYyPiSn7db06CGhygt3Q4zNgWBLFynjSJxKrdqp8vBGJExxgptRnlzJB83kc0ztWVeBUtjMf3eXVzciBUhHqr9q5qY5pF~VDjKGMRk1nEQlIQD04HSgLeAAsz2DvAGnjZ-pZ2PY4sSQwlldj9Y89gE8BlSdmNdW1APE3mXQMSFjxGRkywPCB4MRxwR-LE9QqKIdBl~SJpskwYROTR~iG0u5Wh9dGsIDqrUzUREHs-CgOxNlwdHJXgvf~ojdE-EWZQetOFcOg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":24731,"name":"Apoptosis","url":"https://www.academia.edu/Documents/in/Apoptosis"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":50841,"name":"Caspases","url":"https://www.academia.edu/Documents/in/Caspases"},{"id":74780,"name":"Mutation","url":"https://www.academia.edu/Documents/in/Mutation"},{"id":78116,"name":"Legionella pneumophila","url":"https://www.academia.edu/Documents/in/Legionella_pneumophila"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":102637,"name":"Salmonella Typhimurium","url":"https://www.academia.edu/Documents/in/Salmonella_Typhimurium"},{"id":234980,"name":"NADPH oxidase","url":"https://www.academia.edu/Documents/in/NADPH_oxidase"},{"id":335983,"name":"Lipopolysaccharides","url":"https://www.academia.edu/Documents/in/Lipopolysaccharides"},{"id":1166930,"name":"Cytoplasm","url":"https://www.academia.edu/Documents/in/Cytoplasm"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":3464694,"name":"Macrophage activation","url":"https://www.academia.edu/Documents/in/Macrophage_activation"},{"id":3933647,"name":"Legionnaires Disease","url":"https://www.academia.edu/Documents/in/Legionnaires_Disease-1"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101339-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101336"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101336/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins"><img alt="Research paper thumbnail of IRG and GBP Host Resistance Factors Target Aberrant, “Non-self” Vacuoles Characterized by the Missing of “Self” IRGM Proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/73195666/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101336/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins">IRG and GBP Host Resistance Factors Target Aberrant, “Non-self” Vacuoles Characterized by the Missing of “Self” IRGM Proteins</a></div><div class="wp-workCard_item"><span>PLoS Pathogens</span><span>, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with ''non-self'' PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on ''self'' organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="eaa28ecf37ba5679b7c6e28895b7cd9e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195666,"asset_id":59101336,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195666/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101336"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101336"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101336; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101336]").text(description); $(".js-view-count[data-work-id=59101336]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101336; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101336']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "eaa28ecf37ba5679b7c6e28895b7cd9e" } } $('.js-work-strip[data-work-id=59101336]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101336,"title":"IRG and GBP Host Resistance Factors Target Aberrant, “Non-self” Vacuoles Characterized by the Missing of “Self” IRGM Proteins","translated_title":"","metadata":{"publisher":"Public Library of Science (PLoS)","grobid_abstract":"Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with ''non-self'' PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on ''self'' organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.","publication_date":{"day":null,"month":null,"year":2013,"errors":{}},"publication_name":"PLoS Pathogens","grobid_abstract_attachment_id":73195666},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101336/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins","translated_internal_url":"","created_at":"2021-10-20T04:19:28.911-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195666,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195666/thumbnails/1.jpg","file_name":"3be1431048b2f7aa190c3581fdaacbba1c9a.pdf","download_url":"https://www.academia.edu/attachments/73195666/download_file","bulk_download_file_name":"IRG_and_GBP_Host_Resistance_Factors_Targ.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195666/3be1431048b2f7aa190c3581fdaacbba1c9a-libre.pdf?1634732272=\u0026response-content-disposition=attachment%3B+filename%3DIRG_and_GBP_Host_Resistance_Factors_Targ.pdf\u0026Expires=1743659393\u0026Signature=cV2Il0xZMa8ttI3FPiUhb9NvQtZf5KDxSHjLIk~8iPh3VOnU6OK72dzBcm0h69~zWwmhEea8Lexgtk7ExuY2Eq3cgJ~hhtKmZUOT~FgDRJHtf5mF477eGY5PcRsxHRWb3ib1G1mhtOt1vEAtrsXXlcW18zzwqh0VABsFpJuTGUnj82dFp9NPsMcqimHURYpb2C-644urpYfuN59aJlbE18mmXKHzZibJ57w5k7VAceWG5sGmEekh-VRjCdnKncF20-bKkrjs590IybYwaeRODvhrxx2rUsocuQhsO0FeGbr1uZIG02Rv62z~t79k8~YyEgGf~BVw4hFbO3u8gxhgLw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins","translated_slug":"","page_count":16,"language":"en","content_type":"Work","summary":"Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with ''non-self'' PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on ''self'' organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195666,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195666/thumbnails/1.jpg","file_name":"3be1431048b2f7aa190c3581fdaacbba1c9a.pdf","download_url":"https://www.academia.edu/attachments/73195666/download_file","bulk_download_file_name":"IRG_and_GBP_Host_Resistance_Factors_Targ.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195666/3be1431048b2f7aa190c3581fdaacbba1c9a-libre.pdf?1634732272=\u0026response-content-disposition=attachment%3B+filename%3DIRG_and_GBP_Host_Resistance_Factors_Targ.pdf\u0026Expires=1743659393\u0026Signature=cV2Il0xZMa8ttI3FPiUhb9NvQtZf5KDxSHjLIk~8iPh3VOnU6OK72dzBcm0h69~zWwmhEea8Lexgtk7ExuY2Eq3cgJ~hhtKmZUOT~FgDRJHtf5mF477eGY5PcRsxHRWb3ib1G1mhtOt1vEAtrsXXlcW18zzwqh0VABsFpJuTGUnj82dFp9NPsMcqimHURYpb2C-644urpYfuN59aJlbE18mmXKHzZibJ57w5k7VAceWG5sGmEekh-VRjCdnKncF20-bKkrjs590IybYwaeRODvhrxx2rUsocuQhsO0FeGbr1uZIG02Rv62z~t79k8~YyEgGf~BVw4hFbO3u8gxhgLw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology"},{"id":6947,"name":"Medical Microbiology","url":"https://www.academia.edu/Documents/in/Medical_Microbiology"},{"id":13346,"name":"Toxoplasma","url":"https://www.academia.edu/Documents/in/Toxoplasma"},{"id":24706,"name":"Innate immunity","url":"https://www.academia.edu/Documents/in/Innate_immunity"},{"id":34106,"name":"Chlamydia trachomatis","url":"https://www.academia.edu/Documents/in/Chlamydia_trachomatis"},{"id":37798,"name":"Toxoplasmosis","url":"https://www.academia.edu/Documents/in/Toxoplasmosis"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":2428330,"name":"Vacuoles","url":"https://www.academia.edu/Documents/in/Vacuoles"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101336-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101334"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101334/Leishmania_donovani_Isolates_with_Antimony_Resistant_but_Not_Sensitive_Phenotype_Inhibit_Sodium_Antimony_Gluconate_Induced_Dendritic_Cell_Activation"><img alt="Research paper thumbnail of Leishmania donovani Isolates with Antimony-Resistant but Not -Sensitive Phenotype Inhibit Sodium Antimony Gluconate-Induced Dendritic Cell Activation" class="work-thumbnail" src="https://attachments.academia-assets.com/73195785/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101334/Leishmania_donovani_Isolates_with_Antimony_Resistant_but_Not_Sensitive_Phenotype_Inhibit_Sodium_Antimony_Gluconate_Induced_Dendritic_Cell_Activation">Leishmania donovani Isolates with Antimony-Resistant but Not -Sensitive Phenotype Inhibit Sodium Antimony Gluconate-Induced Dendritic Cell Activation</a></div><div class="wp-workCard_item"><span>PLoS Pathogens</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishma...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishmania donovani (LD) infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs) typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (Sb R LD) and antimony-sensitive (Sb S LD) was compared in vitro. Unlike Sb S LD, infection of DCs with Sb R LD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. Sb R LD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-kB pathways. In contrast, Sb S LD failed to block activation of SAG (20 mg/ml)-induced PI3K/AKT pathway; which continued to stimulate NF-kB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with Sb S LD also inhibited SAG (20 mg/ml)-induced activation of PI3K/AKT and NF-kB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 mg/ml. In contrast, Sb R LD inhibited these SAG-induced events regardless of duration of DC exposure to Sb R LD or dose of SAG. Interestingly, the inhibitory effects of isogenic Sb S LD expressing ATP-binding cassette (ABC) transporter MRPA on SAG-induced leishmanicidal effects mimicked that of Sb R LD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-kB was found to transcriptionally regulate expression of murine cglutamylcysteine synthetase heavy-chain (mcGCS hc) gene, presumably an important regulator of antimony resistance. Importantly, Sb R LD but not Sb S LD blocked SAG-induced mcGCS expression in DCs by preventing NF-kB binding to the mcGCS hc promoter. Our findings demonstrate that Sb R LD but not Sb S LD prevents SAG-induced DC activation by suppressing a PI3K-dependent NF-kB pathway and provide the evidence for differential host-pathogen interaction mediated by Sb R LD and Sb S LD.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="862421b26a570e8e306fd29a66f41ea1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195785,"asset_id":59101334,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195785/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101334"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101334"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101334; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101334]").text(description); $(".js-view-count[data-work-id=59101334]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101334; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101334']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "862421b26a570e8e306fd29a66f41ea1" } } $('.js-work-strip[data-work-id=59101334]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101334,"title":"Leishmania donovani Isolates with Antimony-Resistant but Not -Sensitive Phenotype Inhibit Sodium Antimony Gluconate-Induced Dendritic Cell Activation","translated_title":"","metadata":{"publisher":"Public Library of Science (PLoS)","grobid_abstract":"The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishmania donovani (LD) infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs) typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (Sb R LD) and antimony-sensitive (Sb S LD) was compared in vitro. Unlike Sb S LD, infection of DCs with Sb R LD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. Sb R LD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-kB pathways. In contrast, Sb S LD failed to block activation of SAG (20 mg/ml)-induced PI3K/AKT pathway; which continued to stimulate NF-kB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with Sb S LD also inhibited SAG (20 mg/ml)-induced activation of PI3K/AKT and NF-kB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 mg/ml. In contrast, Sb R LD inhibited these SAG-induced events regardless of duration of DC exposure to Sb R LD or dose of SAG. Interestingly, the inhibitory effects of isogenic Sb S LD expressing ATP-binding cassette (ABC) transporter MRPA on SAG-induced leishmanicidal effects mimicked that of Sb R LD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-kB was found to transcriptionally regulate expression of murine cglutamylcysteine synthetase heavy-chain (mcGCS hc) gene, presumably an important regulator of antimony resistance. Importantly, Sb R LD but not Sb S LD blocked SAG-induced mcGCS expression in DCs by preventing NF-kB binding to the mcGCS hc promoter. Our findings demonstrate that Sb R LD but not Sb S LD prevents SAG-induced DC activation by suppressing a PI3K-dependent NF-kB pathway and provide the evidence for differential host-pathogen interaction mediated by Sb R LD and Sb S LD.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"PLoS Pathogens","grobid_abstract_attachment_id":73195785},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101334/Leishmania_donovani_Isolates_with_Antimony_Resistant_but_Not_Sensitive_Phenotype_Inhibit_Sodium_Antimony_Gluconate_Induced_Dendritic_Cell_Activation","translated_internal_url":"","created_at":"2021-10-20T04:19:28.806-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195785,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195785/thumbnails/1.jpg","file_name":"11d88a9f0220f1a1f03e83345a24b0808f36.pdf","download_url":"https://www.academia.edu/attachments/73195785/download_file","bulk_download_file_name":"Leishmania_donovani_Isolates_with_Antimo.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195785/11d88a9f0220f1a1f03e83345a24b0808f36-libre.pdf?1634732263=\u0026response-content-disposition=attachment%3B+filename%3DLeishmania_donovani_Isolates_with_Antimo.pdf\u0026Expires=1743659393\u0026Signature=hBLRMmdYDfnAtb35qvE1pY627Sb16T4vY9P8j4gSShfCGO63WtqzGf~VqN4V6F0-11s62~75dBuqtLnCvJxIRJBlFc1FSRDtVrvqiuMMVCkVvoS~nBUb4fylqWeje9JED3ETShIuVMMoTbivEdtvUz2cZvhBIvBwYRbVWu6PoQ62BJKlIV9dGYqNk16WLluw95p10BUmLBcILYPz2YJEcogZIcnByXRJrmu2FwFJNyooBHxQ-r6TTOAgPv3rQBfaCq2JKCm7CSMc71y38g6cLKz5veTi6ls0xHguD-dbQhP7hzG~qqf3Kkpok1EgaExzEAk9DQwMp9monyVls7GHyw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Leishmania_donovani_Isolates_with_Antimony_Resistant_but_Not_Sensitive_Phenotype_Inhibit_Sodium_Antimony_Gluconate_Induced_Dendritic_Cell_Activation","translated_slug":"","page_count":21,"language":"en","content_type":"Work","summary":"The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishmania donovani (LD) infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs) typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (Sb R LD) and antimony-sensitive (Sb S LD) was compared in vitro. Unlike Sb S LD, infection of DCs with Sb R LD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. Sb R LD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-kB pathways. In contrast, Sb S LD failed to block activation of SAG (20 mg/ml)-induced PI3K/AKT pathway; which continued to stimulate NF-kB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with Sb S LD also inhibited SAG (20 mg/ml)-induced activation of PI3K/AKT and NF-kB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 mg/ml. In contrast, Sb R LD inhibited these SAG-induced events regardless of duration of DC exposure to Sb R LD or dose of SAG. Interestingly, the inhibitory effects of isogenic Sb S LD expressing ATP-binding cassette (ABC) transporter MRPA on SAG-induced leishmanicidal effects mimicked that of Sb R LD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-kB was found to transcriptionally regulate expression of murine cglutamylcysteine synthetase heavy-chain (mcGCS hc) gene, presumably an important regulator of antimony resistance. Importantly, Sb R LD but not Sb S LD blocked SAG-induced mcGCS expression in DCs by preventing NF-kB binding to the mcGCS hc promoter. Our findings demonstrate that Sb R LD but not Sb S LD prevents SAG-induced DC activation by suppressing a PI3K-dependent NF-kB pathway and provide the evidence for differential host-pathogen interaction mediated by Sb R LD and Sb S LD.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195785,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195785/thumbnails/1.jpg","file_name":"11d88a9f0220f1a1f03e83345a24b0808f36.pdf","download_url":"https://www.academia.edu/attachments/73195785/download_file","bulk_download_file_name":"Leishmania_donovani_Isolates_with_Antimo.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195785/11d88a9f0220f1a1f03e83345a24b0808f36-libre.pdf?1634732263=\u0026response-content-disposition=attachment%3B+filename%3DLeishmania_donovani_Isolates_with_Antimo.pdf\u0026Expires=1743659393\u0026Signature=hBLRMmdYDfnAtb35qvE1pY627Sb16T4vY9P8j4gSShfCGO63WtqzGf~VqN4V6F0-11s62~75dBuqtLnCvJxIRJBlFc1FSRDtVrvqiuMMVCkVvoS~nBUb4fylqWeje9JED3ETShIuVMMoTbivEdtvUz2cZvhBIvBwYRbVWu6PoQ62BJKlIV9dGYqNk16WLluw95p10BUmLBcILYPz2YJEcogZIcnByXRJrmu2FwFJNyooBHxQ-r6TTOAgPv3rQBfaCq2JKCm7CSMc71y38g6cLKz5veTi6ls0xHguD-dbQhP7hzG~qqf3Kkpok1EgaExzEAk9DQwMp9monyVls7GHyw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":1290,"name":"Immunology","url":"https://www.academia.edu/Documents/in/Immunology"},{"id":6947,"name":"Medical Microbiology","url":"https://www.academia.edu/Documents/in/Medical_Microbiology"},{"id":27784,"name":"Gene expression","url":"https://www.academia.edu/Documents/in/Gene_expression"},{"id":35539,"name":"Dendritic Cells","url":"https://www.academia.edu/Documents/in/Dendritic_Cells"},{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":102583,"name":"Drug Resistance","url":"https://www.academia.edu/Documents/in/Drug_Resistance"},{"id":128006,"name":"Sodium Antimony Gluconate","url":"https://www.academia.edu/Documents/in/Sodium_Antimony_Gluconate"},{"id":142138,"name":"Host-parasite interactions","url":"https://www.academia.edu/Documents/in/Host-parasite_interactions"},{"id":153279,"name":"Dendritic cell","url":"https://www.academia.edu/Documents/in/Dendritic_cell"},{"id":213897,"name":"Phenotype","url":"https://www.academia.edu/Documents/in/Phenotype"},{"id":325838,"name":"Host Pathogen Interaction","url":"https://www.academia.edu/Documents/in/Host_Pathogen_Interaction-1"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin"},{"id":2239983,"name":"Glutamate Cysteine Ligase","url":"https://www.academia.edu/Documents/in/Glutamate_Cysteine_Ligase"},{"id":2971099,"name":"Heavy Chain","url":"https://www.academia.edu/Documents/in/Heavy_Chain"},{"id":3214915,"name":"Cricetinae","url":"https://www.academia.edu/Documents/in/Cricetinae"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101334-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101331"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101331/Activation_of_macrophages_and_lymphocytes_by_methylglyoxal_against_tumor_cells_in_the_host"><img alt="Research paper thumbnail of Activation of macrophages and lymphocytes by methylglyoxal against tumor cells in the host" class="work-thumbnail" src="https://attachments.academia-assets.com/73195674/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101331/Activation_of_macrophages_and_lymphocytes_by_methylglyoxal_against_tumor_cells_in_the_host">Activation of macrophages and lymphocytes by methylglyoxal against tumor cells in the host</a></div><div class="wp-workCard_item"><span>International Immunopharmacology</span><span>, 2008</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular p...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular processes. In particular, it can act selectively against malignant cells. The study described herein was to investigate whether methylglyoxal can enhance the non-specific immunity of the host against tumor cells. Methylglyoxal increased the number of macrophages in the peritoneal cavity of both normal and tumor-bearing mice. It also elevated the phagocytic capacity of macrophages in both these groups of animals. This activation of macrophages was brought about by increased production of Reactive Oxygen Intermediates (ROIs) and Reactive Nitrogen Intermediates (RNIs). The possible mechanism for the production of ROIs and RNIs can be attributed to stimulation of the respiratory burst enzyme NADPH oxidase and iNOS, respectively. IFN-γ, which is a regulatory molecule of iNOS pathway also showed an elevated level by methylglyoxal. TNF-α, which is an important cytokine for oxygen independent killing by macrophage also increased by methylglyoxal in both tumor-bearing and non tumor-bearing animals. Methylglyoxal also played a role in the proliferation and cytotoxicity of splenic lymphocytes. In short, it can be concluded that methylglyoxal profoundly stimulates the immune system against tumor cells.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="9c81bd0f604b1cbe1b25d28af2c6a282" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195674,"asset_id":59101331,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195674/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101331"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101331"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101331; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101331]").text(description); $(".js-view-count[data-work-id=59101331]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101331; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101331']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "9c81bd0f604b1cbe1b25d28af2c6a282" } } $('.js-work-strip[data-work-id=59101331]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101331,"title":"Activation of macrophages and lymphocytes by methylglyoxal against tumor cells in the host","translated_title":"","metadata":{"publisher":"Elsevier BV","ai_title_tag":"Methylglyoxal Enhances Immune Response Against Tumors","grobid_abstract":"Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular processes. In particular, it can act selectively against malignant cells. The study described herein was to investigate whether methylglyoxal can enhance the non-specific immunity of the host against tumor cells. Methylglyoxal increased the number of macrophages in the peritoneal cavity of both normal and tumor-bearing mice. It also elevated the phagocytic capacity of macrophages in both these groups of animals. This activation of macrophages was brought about by increased production of Reactive Oxygen Intermediates (ROIs) and Reactive Nitrogen Intermediates (RNIs). The possible mechanism for the production of ROIs and RNIs can be attributed to stimulation of the respiratory burst enzyme NADPH oxidase and iNOS, respectively. IFN-γ, which is a regulatory molecule of iNOS pathway also showed an elevated level by methylglyoxal. TNF-α, which is an important cytokine for oxygen independent killing by macrophage also increased by methylglyoxal in both tumor-bearing and non tumor-bearing animals. Methylglyoxal also played a role in the proliferation and cytotoxicity of splenic lymphocytes. In short, it can be concluded that methylglyoxal profoundly stimulates the immune system against tumor cells.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"International Immunopharmacology","grobid_abstract_attachment_id":73195674},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101331/Activation_of_macrophages_and_lymphocytes_by_methylglyoxal_against_tumor_cells_in_the_host","translated_internal_url":"","created_at":"2021-10-20T04:19:28.652-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195674,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195674/thumbnails/1.jpg","file_name":"j.intimp.2008.06.00520211020-1303-15cc4vl.pdf","download_url":"https://www.academia.edu/attachments/73195674/download_file","bulk_download_file_name":"Activation_of_macrophages_and_lymphocyte.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195674/j.intimp.2008.06.00520211020-1303-15cc4vl-libre.pdf?1634732267=\u0026response-content-disposition=attachment%3B+filename%3DActivation_of_macrophages_and_lymphocyte.pdf\u0026Expires=1743659393\u0026Signature=JeP6v8hoRiYRxf2v1Kkn-XUtNb~6wY8uw15KN2zwGPIm8cAETi2DTXt-5CNvAjJTFE~rMfTC6KTWLjbgXQ8gzLzE8Z43ZR~tGdWMxJe2abWs-Eg9z3O1bsYoPekUa08dayoxC4O91TEwDJWTcdfjRVY2C9GFbyIgLj~jKsV~ZBpCjAblvBuBVtKGcnvNx2H8OoW25ucOq-GIQs~b7ATbr449CYiyRPFImcPmprEiDe4sGcooB~MdNPUqC7xOjmOxpMENNzeF-3hbBDps~kIjXzU7o-Io5MfB7hb~GjiGTtJy2VxcxJshjWScNoQrSYFLLA0RQintldYrsM7tzbDOsw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Activation_of_macrophages_and_lymphocytes_by_methylglyoxal_against_tumor_cells_in_the_host","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular processes. In particular, it can act selectively against malignant cells. The study described herein was to investigate whether methylglyoxal can enhance the non-specific immunity of the host against tumor cells. Methylglyoxal increased the number of macrophages in the peritoneal cavity of both normal and tumor-bearing mice. It also elevated the phagocytic capacity of macrophages in both these groups of animals. This activation of macrophages was brought about by increased production of Reactive Oxygen Intermediates (ROIs) and Reactive Nitrogen Intermediates (RNIs). The possible mechanism for the production of ROIs and RNIs can be attributed to stimulation of the respiratory burst enzyme NADPH oxidase and iNOS, respectively. IFN-γ, which is a regulatory molecule of iNOS pathway also showed an elevated level by methylglyoxal. TNF-α, which is an important cytokine for oxygen independent killing by macrophage also increased by methylglyoxal in both tumor-bearing and non tumor-bearing animals. Methylglyoxal also played a role in the proliferation and cytotoxicity of splenic lymphocytes. In short, it can be concluded that methylglyoxal profoundly stimulates the immune system against tumor cells.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195674,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195674/thumbnails/1.jpg","file_name":"j.intimp.2008.06.00520211020-1303-15cc4vl.pdf","download_url":"https://www.academia.edu/attachments/73195674/download_file","bulk_download_file_name":"Activation_of_macrophages_and_lymphocyte.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195674/j.intimp.2008.06.00520211020-1303-15cc4vl-libre.pdf?1634732267=\u0026response-content-disposition=attachment%3B+filename%3DActivation_of_macrophages_and_lymphocyte.pdf\u0026Expires=1743659393\u0026Signature=JeP6v8hoRiYRxf2v1Kkn-XUtNb~6wY8uw15KN2zwGPIm8cAETi2DTXt-5CNvAjJTFE~rMfTC6KTWLjbgXQ8gzLzE8Z43ZR~tGdWMxJe2abWs-Eg9z3O1bsYoPekUa08dayoxC4O91TEwDJWTcdfjRVY2C9GFbyIgLj~jKsV~ZBpCjAblvBuBVtKGcnvNx2H8OoW25ucOq-GIQs~b7ATbr449CYiyRPFImcPmprEiDe4sGcooB~MdNPUqC7xOjmOxpMENNzeF-3hbBDps~kIjXzU7o-Io5MfB7hb~GjiGTtJy2VxcxJshjWScNoQrSYFLLA0RQintldYrsM7tzbDOsw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":26699,"name":"Immunopharmacology","url":"https://www.academia.edu/Documents/in/Immunopharmacology"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":118793,"name":"Sarcoma","url":"https://www.academia.edu/Documents/in/Sarcoma"},{"id":231661,"name":"Enzyme","url":"https://www.academia.edu/Documents/in/Enzyme"},{"id":234980,"name":"NADPH oxidase","url":"https://www.academia.edu/Documents/in/NADPH_oxidase"},{"id":324154,"name":"Immune system","url":"https://www.academia.edu/Documents/in/Immune_system"},{"id":474029,"name":"Tumor necrosis factor-alpha","url":"https://www.academia.edu/Documents/in/Tumor_necrosis_factor-alpha"},{"id":782251,"name":"Cell Proliferation","url":"https://www.academia.edu/Documents/in/Cell_Proliferation"},{"id":868560,"name":"Lymphocytes","url":"https://www.academia.edu/Documents/in/Lymphocytes"},{"id":1212103,"name":"Antineoplastic Agents","url":"https://www.academia.edu/Documents/in/Antineoplastic_Agents"},{"id":1455811,"name":"Superoxides","url":"https://www.academia.edu/Documents/in/Superoxides"},{"id":1626171,"name":"Respiratory Burst","url":"https://www.academia.edu/Documents/in/Respiratory_Burst"},{"id":1654024,"name":"Nitrites","url":"https://www.academia.edu/Documents/in/Nitrites"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":3464694,"name":"Macrophage activation","url":"https://www.academia.edu/Documents/in/Macrophage_activation"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101331-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101328"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101328/Designing_Therapies_against_Experimental_Visceral_Leishmaniasis_by_Modulating_the_Membrane_Fluidity_of_Antigen_Presenting_Cells"><img alt="Research paper thumbnail of Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells" class="work-thumbnail" src="https://attachments.academia-assets.com/73195787/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101328/Designing_Therapies_against_Experimental_Visceral_Leishmaniasis_by_Modulating_the_Membrane_Fluidity_of_Antigen_Presenting_Cells">Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells</a></div><div class="wp-workCard_item"><span>Infection and Immunity</span><span>, 2009</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The membrane fluidity of antigen-presenting cells (APCs) has a significant bearing on T-cell-stim...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The membrane fluidity of antigen-presenting cells (APCs) has a significant bearing on T-cell-stimulating ability and is dependent on the cholesterol content of the membrane. The relationship, if any, between membrane fluidity and defective cell-mediated immunity in visceral leishmaniasis has been investigated. Systemic administration of cholesterol by liposome delivery (cholesterol liposomes) in Leishmania donovani -infected hamsters was found to cure the infection. Splenic macrophages as a prototype of APCs in infected hamsters had decreased membrane cholesterol and an inability to drive T cells, which was corrected by cholesterol liposome treatment. The effect was cholesterol specific because liposomes made up of the analogue 4-cholesten-3-one provided almost no protection. Infection led to increases in interleukin-10 (IL-10), transforming growth factor beta, and IL-4 signals and concomitant decreases in gamma interferon (IFN-γ), tumor necrosis factor alpha, and inducible NO synth...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="0f85d6909de9cbe9281d5adec4553d79" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195787,"asset_id":59101328,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195787/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101328"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101328"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101328; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101328]").text(description); $(".js-view-count[data-work-id=59101328]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101328; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101328']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "0f85d6909de9cbe9281d5adec4553d79" } } $('.js-work-strip[data-work-id=59101328]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101328,"title":"Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells","translated_title":"","metadata":{"abstract":"The membrane fluidity of antigen-presenting cells (APCs) has a significant bearing on T-cell-stimulating ability and is dependent on the cholesterol content of the membrane. The relationship, if any, between membrane fluidity and defective cell-mediated immunity in visceral leishmaniasis has been investigated. Systemic administration of cholesterol by liposome delivery (cholesterol liposomes) in Leishmania donovani -infected hamsters was found to cure the infection. Splenic macrophages as a prototype of APCs in infected hamsters had decreased membrane cholesterol and an inability to drive T cells, which was corrected by cholesterol liposome treatment. The effect was cholesterol specific because liposomes made up of the analogue 4-cholesten-3-one provided almost no protection. 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Splenic macrophages as a prototype of APCs in infected hamsters had decreased membrane cholesterol and an inability to drive T cells, which was corrected by cholesterol liposome treatment. The effect was cholesterol specific because liposomes made up of the analogue 4-cholesten-3-one provided almost no protection. 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Infection led to increases in interleukin-10 (IL-10), transforming growth factor beta, and IL-4 signals and concomitant decreases in gamma interferon (IFN-γ), tumor necrosis factor alpha, and inducible NO synth...","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195787,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195787/thumbnails/1.jpg","file_name":"2330.pdf","download_url":"https://www.academia.edu/attachments/73195787/download_file","bulk_download_file_name":"Designing_Therapies_against_Experimental.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195787/2330-libre.pdf?1634732260=\u0026response-content-disposition=attachment%3B+filename%3DDesigning_Therapies_against_Experimental.pdf\u0026Expires=1743659393\u0026Signature=U513KEQbCPL5rJYbxYOxu-LjaEZKv97l2Uv1BFdEZ-4uKbxIzKXHpmeoXQP-anSsMf66OrNEC6fmd-RchXDUm1ubchVOzEPNQ6h0eO0O2rHW8JIKCYnrAlgnpzI0Ym0-WReY5764VIwmUn6AxFV~yBp~VqVSwReu0FNVm3pYbqOcW0wejBxo6zr-wIYIODWPOVxQMY512YcIFTpM2xcqNy-4mXts17s5MWy95QKcBGDXA~nfVRyFs~2j~08-Pojmpedtlepecqwd24zRKq8jjDiVEhui~-64M7juLndRd58RL8KY0XvoM1tNS2CFySPBfOE~e1-G7I3RNuAgwuu9qg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":2702,"name":"Immune response","url":"https://www.academia.edu/Documents/in/Immune_response"},{"id":9111,"name":"Cytokines","url":"https://www.academia.edu/Documents/in/Cytokines"},{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":19849,"name":"Leishmania","url":"https://www.academia.edu/Documents/in/Leishmania"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":48758,"name":"Infection and immunity","url":"https://www.academia.edu/Documents/in/Infection_and_immunity"},{"id":82978,"name":"Reactive Oxygen Species","url":"https://www.academia.edu/Documents/in/Reactive_Oxygen_Species"},{"id":90514,"name":"Cholesterol","url":"https://www.academia.edu/Documents/in/Cholesterol"},{"id":93922,"name":"Nitric oxide","url":"https://www.academia.edu/Documents/in/Nitric_oxide"},{"id":109739,"name":"Infection","url":"https://www.academia.edu/Documents/in/Infection"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":951344,"name":"Growth Factor","url":"https://www.academia.edu/Documents/in/Growth_Factor"},{"id":1426712,"name":"Immunoglobulin","url":"https://www.academia.edu/Documents/in/Immunoglobulin"},{"id":1465015,"name":"Membrane Fluidity","url":"https://www.academia.edu/Documents/in/Membrane_Fluidity"},{"id":1792514,"name":"Antigen presenting cells","url":"https://www.academia.edu/Documents/in/Antigen_presenting_cells"},{"id":2468093,"name":"Cell Membrane","url":"https://www.academia.edu/Documents/in/Cell_Membrane"},{"id":3196500,"name":"Tumor necrosis factor","url":"https://www.academia.edu/Documents/in/Tumor_necrosis_factor"},{"id":3214915,"name":"Cricetinae","url":"https://www.academia.edu/Documents/in/Cricetinae"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101328-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101326"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101326/Hybrid_Cell_Vaccination_Resolves_Leishmania_donovani_Infection_by_Eliciting_a_Strong_CD8_Cytotoxic_T_Lymphocyte_Response_with_Concomitant_Suppression_of_Interleukin_10_IL_10_but_Not_IL_4_or_IL_13"><img alt="Research paper thumbnail of Hybrid Cell Vaccination Resolves Leishmania donovani Infection by Eliciting a Strong CD8+ Cytotoxic T-Lymphocyte Response with Concomitant Suppression of Interleukin-10 (IL-10) but Not IL-4 or IL-13" class="work-thumbnail" src="https://attachments.academia-assets.com/73195783/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101326/Hybrid_Cell_Vaccination_Resolves_Leishmania_donovani_Infection_by_Eliciting_a_Strong_CD8_Cytotoxic_T_Lymphocyte_Response_with_Concomitant_Suppression_of_Interleukin_10_IL_10_but_Not_IL_4_or_IL_13">Hybrid Cell Vaccination Resolves Leishmania donovani Infection by Eliciting a Strong CD8+ Cytotoxic T-Lymphocyte Response with Concomitant Suppression of Interleukin-10 (IL-10) but Not IL-4 or IL-13</a></div><div class="wp-workCard_item"><span>Infection and Immunity</span><span>, 2007</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">There is an acute dearth of therapeutic interventions against visceral leishmaniasis that is requ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">There is an acute dearth of therapeutic interventions against visceral leishmaniasis that is required to restore an established defective cell-mediated immune response. Hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. We implemented hybrid cell vaccination therapy in Leishmania donovani-infected BALB/c mice by electrofusing dominant Leishmania antigen kinetoplastid membrane protein 11 (KMP-11)-transfected bone marrow-derived macrophages from BALB/c mice with allogeneic bone marrow-derived dendritic cells from C57BL/6 mice. Hybrid cell vaccine (HCV) cleared the splenic and hepatic parasite burden, eliciting KMP-11-specific major histocompatibility complex class I-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses. Moreover, splenic lymphocytes of HCV-treated mice not only showed the enhancement of gamma interferon but also marked an elevated expression of the Th2 cytokines i...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="618f701907081dd5bb3f724505821fc0" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195783,"asset_id":59101326,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195783/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101326"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101326"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101326; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101326]").text(description); $(".js-view-count[data-work-id=59101326]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101326; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101326']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "618f701907081dd5bb3f724505821fc0" } } $('.js-work-strip[data-work-id=59101326]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101326,"title":"Hybrid Cell Vaccination Resolves Leishmania donovani Infection by Eliciting a Strong CD8+ Cytotoxic T-Lymphocyte Response with Concomitant Suppression of Interleukin-10 (IL-10) but Not IL-4 or IL-13","translated_title":"","metadata":{"abstract":"There is an acute dearth of therapeutic interventions against visceral leishmaniasis that is required to restore an established defective cell-mediated immune response. Hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. We implemented hybrid cell vaccination therapy in Leishmania donovani-infected BALB/c mice by electrofusing dominant Leishmania antigen kinetoplastid membrane protein 11 (KMP-11)-transfected bone marrow-derived macrophages from BALB/c mice with allogeneic bone marrow-derived dendritic cells from C57BL/6 mice. Hybrid cell vaccine (HCV) cleared the splenic and hepatic parasite burden, eliciting KMP-11-specific major histocompatibility complex class I-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses. Moreover, splenic lymphocytes of HCV-treated mice not only showed the enhancement of gamma interferon but also marked an elevated expression of the Th2 cytokines i...","publisher":"American Society for Microbiology","ai_title_tag":"Hybrid Cell Vaccination against Leishmania","publication_date":{"day":null,"month":null,"year":2007,"errors":{}},"publication_name":"Infection and Immunity"},"translated_abstract":"There is an acute dearth of therapeutic interventions against visceral leishmaniasis that is required to restore an established defective cell-mediated immune response. Hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. We implemented hybrid cell vaccination therapy in Leishmania donovani-infected BALB/c mice by electrofusing dominant Leishmania antigen kinetoplastid membrane protein 11 (KMP-11)-transfected bone marrow-derived macrophages from BALB/c mice with allogeneic bone marrow-derived dendritic cells from C57BL/6 mice. Hybrid cell vaccine (HCV) cleared the splenic and hepatic parasite burden, eliciting KMP-11-specific major histocompatibility complex class I-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses. 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Hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. We implemented hybrid cell vaccination therapy in Leishmania donovani-infected BALB/c mice by electrofusing dominant Leishmania antigen kinetoplastid membrane protein 11 (KMP-11)-transfected bone marrow-derived macrophages from BALB/c mice with allogeneic bone marrow-derived dendritic cells from C57BL/6 mice. Hybrid cell vaccine (HCV) cleared the splenic and hepatic parasite burden, eliciting KMP-11-specific major histocompatibility complex class I-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101326-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101323"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101323/Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_%CE%B3_to_IL_10_ratio"><img alt="Research paper thumbnail of Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio" class="work-thumbnail" src="https://attachments.academia-assets.com/73195813/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101323/Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_%CE%B3_to_IL_10_ratio">Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio</a></div><div class="wp-workCard_item"><span>Experimental Parasitology</span><span>, 2009</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and t...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O 2) 2 (H 2 O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb R) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-c and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-c inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="835de0aeffe0c9db846396e9e10541a7" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195813,"asset_id":59101323,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195813/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101323"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101323"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101323; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101323]").text(description); $(".js-view-count[data-work-id=59101323]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101323; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101323']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "835de0aeffe0c9db846396e9e10541a7" } } $('.js-work-strip[data-work-id=59101323]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101323,"title":"Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio","translated_title":"","metadata":{"publisher":"Elsevier BV","ai_title_tag":"SAG-PV6 Combo Treats Antimony Resistant Leishmaniasis","grobid_abstract":"We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O 2) 2 (H 2 O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb R) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-c and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-c inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.","publication_date":{"day":null,"month":null,"year":2009,"errors":{}},"publication_name":"Experimental Parasitology","grobid_abstract_attachment_id":73195813},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101323/Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_%CE%B3_to_IL_10_ratio","translated_internal_url":"","created_at":"2021-10-20T04:19:28.348-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195813,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195813/thumbnails/1.jpg","file_name":"j.exppara.2009.02.00120211020-1300-5rueab.pdf","download_url":"https://www.academia.edu/attachments/73195813/download_file","bulk_download_file_name":"Sub_optimal_dose_of_Sodium_Antimony_Gluc.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195813/j.exppara.2009.02.00120211020-1300-5rueab-libre.pdf?1634732259=\u0026response-content-disposition=attachment%3B+filename%3DSub_optimal_dose_of_Sodium_Antimony_Gluc.pdf\u0026Expires=1743659393\u0026Signature=KIiW~rhxwQDr9DgO49heGmIpdGzc~zl5LV52tnN~lcVctjVLsGdzeqvuSo-wLWPe2NI66dQT86-llJYmp14wQxARX~OZWynislO5lVWj-Qs-23qhxEA4c6diNWbta7NTVYAACWeCJw7yr0QagxlrM1XyJ6i5oIaATrG7lNBJog7kbuClTHxcPsMGJcp7Y4rSp9Chki7HArm5iPWSchVQ9jxHhrcsoXhK9hIRbhBT4MlHSsj8W8D8GGQlJMZ5eCTtvmzf5MWSiJykqzdl5KumKyDcTqT5wu2eWFQmmGBmUahRL6-Dkv3np6K-lesbxlJpOIuGe6MWya~AZw2JcUZwFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Sub_optimal_dose_of_Sodium_Antimony_Gluconate_SAG_diperoxovanadate_combination_clears_organ_parasites_from_BALB_c_mice_infected_with_antimony_resistant_Leishmania_donovani_by_expanding_antileishmanial_T_cell_repertoire_and_increasing_IFN_γ_to_IL_10_ratio","translated_slug":"","page_count":10,"language":"en","content_type":"Work","summary":"We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O 2) 2 (H 2 O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb R) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-c and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-c inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195813,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195813/thumbnails/1.jpg","file_name":"j.exppara.2009.02.00120211020-1300-5rueab.pdf","download_url":"https://www.academia.edu/attachments/73195813/download_file","bulk_download_file_name":"Sub_optimal_dose_of_Sodium_Antimony_Gluc.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195813/j.exppara.2009.02.00120211020-1300-5rueab-libre.pdf?1634732259=\u0026response-content-disposition=attachment%3B+filename%3DSub_optimal_dose_of_Sodium_Antimony_Gluc.pdf\u0026Expires=1743659393\u0026Signature=KIiW~rhxwQDr9DgO49heGmIpdGzc~zl5LV52tnN~lcVctjVLsGdzeqvuSo-wLWPe2NI66dQT86-llJYmp14wQxARX~OZWynislO5lVWj-Qs-23qhxEA4c6diNWbta7NTVYAACWeCJw7yr0QagxlrM1XyJ6i5oIaATrG7lNBJog7kbuClTHxcPsMGJcp7Y4rSp9Chki7HArm5iPWSchVQ9jxHhrcsoXhK9hIRbhBT4MlHSsj8W8D8GGQlJMZ5eCTtvmzf5MWSiJykqzdl5KumKyDcTqT5wu2eWFQmmGBmUahRL6-Dkv3np6K-lesbxlJpOIuGe6MWya~AZw2JcUZwFg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":49018,"name":"Spleen","url":"https://www.academia.edu/Documents/in/Spleen"},{"id":53307,"name":"Experimental parasitology","url":"https://www.academia.edu/Documents/in/Experimental_parasitology"},{"id":71437,"name":"Liver","url":"https://www.academia.edu/Documents/in/Liver"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":93922,"name":"Nitric oxide","url":"https://www.academia.edu/Documents/in/Nitric_oxide"},{"id":94271,"name":"Parasite","url":"https://www.academia.edu/Documents/in/Parasite"},{"id":102583,"name":"Drug Resistance","url":"https://www.academia.edu/Documents/in/Drug_Resistance"},{"id":128006,"name":"Sodium Antimony Gluconate","url":"https://www.academia.edu/Documents/in/Sodium_Antimony_Gluconate"},{"id":203750,"name":"Dose","url":"https://www.academia.edu/Documents/in/Dose"},{"id":238630,"name":"Experimental Infection","url":"https://www.academia.edu/Documents/in/Experimental_Infection"},{"id":280237,"name":"T lymphocytes","url":"https://www.academia.edu/Documents/in/T_lymphocytes"},{"id":329844,"name":"Experimental","url":"https://www.academia.edu/Documents/in/Experimental"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"},{"id":1455811,"name":"Superoxides","url":"https://www.academia.edu/Documents/in/Superoxides"},{"id":1924712,"name":"Interleukin","url":"https://www.academia.edu/Documents/in/Interleukin"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":3094724,"name":"Peroxides","url":"https://www.academia.edu/Documents/in/Peroxides"},{"id":3214915,"name":"Cricetinae","url":"https://www.academia.edu/Documents/in/Cricetinae"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101323-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101321"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101321/Radio_attenuated_leishmanial_parasites_as_immunoprophylactic_agent_against_experimental_murine_visceral_leishmaniasis"><img alt="Research paper thumbnail of Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis" class="work-thumbnail" src="https://attachments.academia-assets.com/73195682/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101321/Radio_attenuated_leishmanial_parasites_as_immunoprophylactic_agent_against_experimental_murine_visceral_leishmaniasis">Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis</a></div><div class="wp-workCard_item"><span>Experimental Parasitology</span><span>, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The present study intends to evaluate the role of radio-attenuated leishmania parasites as immuno...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The present study intends to evaluate the role of radio-attenuated leishmania parasites as immunoprophylactic agents for experimental murine visceral leishmaniasis. BALB/c mice were immunized with gamma (c)-irradiated Leishmania donovani. A second immunization was given after 15 days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimental groups. It was observed that BALB/c mice having prior immunization with radio-attenuated parasites showed protection against L. donovani infection through higher expression of Th1 cytokines and suppression of Th2 cytokines along with the generation of protective free radicals. The group of mice without prior priming with radio-attenuated parasites surrendered to the disease. Thus it can be concluded that radio-attenuated L. donovani may be used for.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="4fa1fd854a5c56926c25bcd99017fdec" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195682,"asset_id":59101321,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195682/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101321"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101321"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101321; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101321]").text(description); $(".js-view-count[data-work-id=59101321]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101321; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101321']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "4fa1fd854a5c56926c25bcd99017fdec" } } $('.js-work-strip[data-work-id=59101321]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101321,"title":"Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis","translated_title":"","metadata":{"publisher":"Elsevier BV","ai_title_tag":"Immunization with Radio-Attenuated Leishmania Against Visceral Leishmaniasis","grobid_abstract":"The present study intends to evaluate the role of radio-attenuated leishmania parasites as immunoprophylactic agents for experimental murine visceral leishmaniasis. BALB/c mice were immunized with gamma (c)-irradiated Leishmania donovani. A second immunization was given after 15 days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimental groups. It was observed that BALB/c mice having prior immunization with radio-attenuated parasites showed protection against L. donovani infection through higher expression of Th1 cytokines and suppression of Th2 cytokines along with the generation of protective free radicals. The group of mice without prior priming with radio-attenuated parasites surrendered to the disease. 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BALB/c mice were immunized with gamma (c)-irradiated Leishmania donovani. A second immunization was given after 15 days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimental groups. It was observed that BALB/c mice having prior immunization with radio-attenuated parasites showed protection against L. donovani infection through higher expression of Th1 cytokines and suppression of Th2 cytokines along with the generation of protective free radicals. The group of mice without prior priming with radio-attenuated parasites surrendered to the disease. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101321-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="59101113"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/59101113/The_E2_Like_Conjugation_Enzyme_Atg3_Promotes_Binding_of_IRG_and_Gbp_Proteins_to_Chlamydia_and_Toxoplasma_Containing_Vacuoles_and_Host_Resistance"><img alt="Research paper thumbnail of The E2-Like Conjugation Enzyme Atg3 Promotes Binding of IRG and Gbp Proteins to Chlamydia- and Toxoplasma-Containing Vacuoles and Host Resistance" class="work-thumbnail" src="https://attachments.academia-assets.com/73195502/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/59101113/The_E2_Like_Conjugation_Enzyme_Atg3_Promotes_Binding_of_IRG_and_Gbp_Proteins_to_Chlamydia_and_Toxoplasma_Containing_Vacuoles_and_Host_Resistance">The E2-Like Conjugation Enzyme Atg3 Promotes Binding of IRG and Gbp Proteins to Chlamydia- and Toxoplasma-Containing Vacuoles and Host Resistance</a></div><div class="wp-workCard_item"><span>PLoS ONE</span><span>, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathog...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathogen Toxoplasma gondii is controlled by two families of Interferon (IFN)-inducible GTPases: Immunity Related GTPases (IRGs) and Guanylate binding proteins (Gbps). Members of these two GTPase families associate with pathogen-containing vacuoles (PVs) and solicit antimicrobial resistance pathways specifically to the intracellular site of infection. The proper delivery of IRG and Gbp proteins to PVs requires the autophagy factor Atg5. Atg5 is part of a protein complex that facilitates the transfer of the ubiquitin-like protein Atg8 from the E2-like conjugation enzyme Atg3 to the lipid phosphatidylethanolamine. Here, we show that Atg3 expression, similar to Atg5 expression, is required for IRG and Gbp proteins to dock to PVs. We further demonstrate that expression of a dominant-active, GTP-locked IRG protein variant rescues the PV targeting defect of Atg3and Atg5-deficient cells, suggesting a possible role for Atg proteins in the activation of IRG proteins. Lastly, we show that IFN-induced cell-autonomous resistance to C. trachomatis infections in mouse cells depends not only on Atg5 and IRG proteins, as previously demonstrated, but also requires the expression of Atg3 and Gbp proteins. These findings provide a foundation for a better understanding of IRG-and Gbp-dependent cell-autonomous resistance and its regulation by Atg proteins.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="06b2bc702bf795b86bd4a61d8c545afa" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":73195502,"asset_id":59101113,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/73195502/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="59101113"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="59101113"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 59101113; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=59101113]").text(description); $(".js-view-count[data-work-id=59101113]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 59101113; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='59101113']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "06b2bc702bf795b86bd4a61d8c545afa" } } $('.js-work-strip[data-work-id=59101113]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":59101113,"title":"The E2-Like Conjugation Enzyme Atg3 Promotes Binding of IRG and Gbp Proteins to Chlamydia- and Toxoplasma-Containing Vacuoles and Host Resistance","translated_title":"","metadata":{"publisher":"Public Library of Science (PLoS)","grobid_abstract":"Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathogen Toxoplasma gondii is controlled by two families of Interferon (IFN)-inducible GTPases: Immunity Related GTPases (IRGs) and Guanylate binding proteins (Gbps). Members of these two GTPase families associate with pathogen-containing vacuoles (PVs) and solicit antimicrobial resistance pathways specifically to the intracellular site of infection. The proper delivery of IRG and Gbp proteins to PVs requires the autophagy factor Atg5. Atg5 is part of a protein complex that facilitates the transfer of the ubiquitin-like protein Atg8 from the E2-like conjugation enzyme Atg3 to the lipid phosphatidylethanolamine. Here, we show that Atg3 expression, similar to Atg5 expression, is required for IRG and Gbp proteins to dock to PVs. We further demonstrate that expression of a dominant-active, GTP-locked IRG protein variant rescues the PV targeting defect of Atg3and Atg5-deficient cells, suggesting a possible role for Atg proteins in the activation of IRG proteins. Lastly, we show that IFN-induced cell-autonomous resistance to C. trachomatis infections in mouse cells depends not only on Atg5 and IRG proteins, as previously demonstrated, but also requires the expression of Atg3 and Gbp proteins. These findings provide a foundation for a better understanding of IRG-and Gbp-dependent cell-autonomous resistance and its regulation by Atg proteins.","publication_date":{"day":null,"month":null,"year":2014,"errors":{}},"publication_name":"PLoS ONE","grobid_abstract_attachment_id":73195502},"translated_abstract":null,"internal_url":"https://www.academia.edu/59101113/The_E2_Like_Conjugation_Enzyme_Atg3_Promotes_Binding_of_IRG_and_Gbp_Proteins_to_Chlamydia_and_Toxoplasma_Containing_Vacuoles_and_Host_Resistance","translated_internal_url":"","created_at":"2021-10-20T04:15:54.474-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":144833746,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":73195502,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195502/thumbnails/1.jpg","file_name":"106d972197e05ab1b51068491caedfb52166.pdf","download_url":"https://www.academia.edu/attachments/73195502/download_file","bulk_download_file_name":"The_E2_Like_Conjugation_Enzyme_Atg3_Prom.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195502/106d972197e05ab1b51068491caedfb52166-libre.pdf?1634732281=\u0026response-content-disposition=attachment%3B+filename%3DThe_E2_Like_Conjugation_Enzyme_Atg3_Prom.pdf\u0026Expires=1743659393\u0026Signature=TPLF8COA24-ynQfk0qFagE6-CwZFJLCaoLqgibX3pKYDPa1EAFrsQRWra7cS79BQcROnc0BG0tBvkiyztcgY2JjH0ykBKwBxM8WrdREpBkZNvOi8g8sAQqfghGQikMw0AWBRJajYFj8JxAE9Lx0IpfvWi4ZnLmZqWsy4QvZog5Ej7rhT8DBlMw9KVpQ5HKWN~jgL26glqRoCL5BHVWaIXZrRaBRrY8YS9NJFu~ZCjxEU8zMIx4LiQhvVAwEishdAdktvZvFrq07x-wF1UMAnCa12mQWBAPy63b3Co7RrnahGY-g1JoJwAIqSchzHV3IxRLRjbuyqTfDRb6sULjCw0Q__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"The_E2_Like_Conjugation_Enzyme_Atg3_Promotes_Binding_of_IRG_and_Gbp_Proteins_to_Chlamydia_and_Toxoplasma_Containing_Vacuoles_and_Host_Resistance","translated_slug":"","page_count":9,"language":"en","content_type":"Work","summary":"Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathogen Toxoplasma gondii is controlled by two families of Interferon (IFN)-inducible GTPases: Immunity Related GTPases (IRGs) and Guanylate binding proteins (Gbps). Members of these two GTPase families associate with pathogen-containing vacuoles (PVs) and solicit antimicrobial resistance pathways specifically to the intracellular site of infection. The proper delivery of IRG and Gbp proteins to PVs requires the autophagy factor Atg5. Atg5 is part of a protein complex that facilitates the transfer of the ubiquitin-like protein Atg8 from the E2-like conjugation enzyme Atg3 to the lipid phosphatidylethanolamine. Here, we show that Atg3 expression, similar to Atg5 expression, is required for IRG and Gbp proteins to dock to PVs. We further demonstrate that expression of a dominant-active, GTP-locked IRG protein variant rescues the PV targeting defect of Atg3and Atg5-deficient cells, suggesting a possible role for Atg proteins in the activation of IRG proteins. Lastly, we show that IFN-induced cell-autonomous resistance to C. trachomatis infections in mouse cells depends not only on Atg5 and IRG proteins, as previously demonstrated, but also requires the expression of Atg3 and Gbp proteins. These findings provide a foundation for a better understanding of IRG-and Gbp-dependent cell-autonomous resistance and its regulation by Atg proteins.","owner":{"id":144833746,"first_name":"Arun","middle_initials":"K","last_name":"Haldar","page_name":"HDrAK","domain_name":"independent","created_at":"2020-02-06T01:21:19.790-08:00","display_name":"Arun K Haldar","url":"https://independent.academia.edu/HDrAK"},"attachments":[{"id":73195502,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/73195502/thumbnails/1.jpg","file_name":"106d972197e05ab1b51068491caedfb52166.pdf","download_url":"https://www.academia.edu/attachments/73195502/download_file","bulk_download_file_name":"The_E2_Like_Conjugation_Enzyme_Atg3_Prom.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/73195502/106d972197e05ab1b51068491caedfb52166-libre.pdf?1634732281=\u0026response-content-disposition=attachment%3B+filename%3DThe_E2_Like_Conjugation_Enzyme_Atg3_Prom.pdf\u0026Expires=1743659393\u0026Signature=TPLF8COA24-ynQfk0qFagE6-CwZFJLCaoLqgibX3pKYDPa1EAFrsQRWra7cS79BQcROnc0BG0tBvkiyztcgY2JjH0ykBKwBxM8WrdREpBkZNvOi8g8sAQqfghGQikMw0AWBRJajYFj8JxAE9Lx0IpfvWi4ZnLmZqWsy4QvZog5Ej7rhT8DBlMw9KVpQ5HKWN~jgL26glqRoCL5BHVWaIXZrRaBRrY8YS9NJFu~ZCjxEU8zMIx4LiQhvVAwEishdAdktvZvFrq07x-wF1UMAnCa12mQWBAPy63b3Co7RrnahGY-g1JoJwAIqSchzHV3IxRLRjbuyqTfDRb6sULjCw0Q__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":48,"name":"Engineering","url":"https://www.academia.edu/Documents/in/Engineering"},{"id":498,"name":"Physics","url":"https://www.academia.edu/Documents/in/Physics"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":13346,"name":"Toxoplasma","url":"https://www.academia.edu/Documents/in/Toxoplasma"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":28235,"name":"Multidisciplinary","url":"https://www.academia.edu/Documents/in/Multidisciplinary"},{"id":34106,"name":"Chlamydia trachomatis","url":"https://www.academia.edu/Documents/in/Chlamydia_trachomatis"},{"id":37798,"name":"Toxoplasmosis","url":"https://www.academia.edu/Documents/in/Toxoplasmosis"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":84924,"name":"Immunity","url":"https://www.academia.edu/Documents/in/Immunity"},{"id":105062,"name":"Disease resistance","url":"https://www.academia.edu/Documents/in/Disease_resistance"},{"id":220780,"name":"PLoS one","url":"https://www.academia.edu/Documents/in/PLoS_one"},{"id":284067,"name":"Inclusion Bodies","url":"https://www.academia.edu/Documents/in/Inclusion_Bodies"},{"id":418954,"name":"Guanosine Triphosphate","url":"https://www.academia.edu/Documents/in/Guanosine_Triphosphate"},{"id":1010725,"name":"Protein Binding","url":"https://www.academia.edu/Documents/in/Protein_Binding"},{"id":1288743,"name":"Gtp Binding Proteins","url":"https://www.academia.edu/Documents/in/Gtp_Binding_Proteins"},{"id":2058663,"name":"Interferon gamma","url":"https://www.academia.edu/Documents/in/Interferon_gamma"},{"id":2428330,"name":"Vacuoles","url":"https://www.academia.edu/Documents/in/Vacuoles"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") if (false) { Aedu.setUpFigureCarousel('profile-work-59101113-figures'); } }); </script> <div class="js-work-strip profile--work_container" data-work-id="53277781"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/53277781/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins"><img alt="Research paper thumbnail of IRG and GBP Host Resistance Factors Target Aberrant, ''Non-self'' Vacuoles Characterized by the Missing of ''Self'' IRGM Proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/70189962/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/53277781/IRG_and_GBP_Host_Resistance_Factors_Target_Aberrant_Non_self_Vacuoles_Characterized_by_the_Missing_of_Self_IRGM_Proteins">IRG and GBP Host Resistance Factors Target Aberrant, ''Non-self'' Vacuoles Characterized by the Missing of ''Self'' IRGM Proteins</a></div><div class="wp-workCard_item"><span>PLoS Pathogens</span><span>, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with ''non-self'' PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on ''self'' organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="be16f4608b659b364a04e655cd9259c8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":70189962,"asset_id":53277781,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/70189962/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="53277781"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="53277781"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 53277781; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=53277781]").text(description); $(".js-view-count[data-work-id=53277781]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 53277781; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='53277781']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "be16f4608b659b364a04e655cd9259c8" } } $('.js-work-strip[data-work-id=53277781]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":53277781,"title":"IRG and GBP Host Resistance Factors Target Aberrant, ''Non-self'' Vacuoles Characterized by the Missing of ''Self'' IRGM Proteins","translated_title":"","metadata":{"abstract":"Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. 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These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of ''self'' IRGM proteins from these structures.","publication_date":{"day":null,"month":null,"year":2013,"errors":{}},"publication_name":"PLoS Pathogens"},"translated_abstract":"Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. 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Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-γ and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-γ inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="3245a5697c3cb876056b8d44312b8030" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":70099751,"asset_id":53198778,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/70099751/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="53198778"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="53198778"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 53198778; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=53198778]").text(description); $(".js-view-count[data-work-id=53198778]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 53198778; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='53198778']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "3245a5697c3cb876056b8d44312b8030" } } $('.js-work-strip[data-work-id=53198778]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":53198778,"title":"Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio","translated_title":"","metadata":{"abstract":"We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O2)2(H2O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (SbR) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. 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