{"id":1315,"date":"2016-09-06T21:25:36","date_gmt":"2016-09-06T21:25:36","guid":{"rendered":"http:\/\/desertkingdev.wpenginepowered.com\/2016\/09\/06\/identification-of-qs-21-as-an-inflammasome-activating-molecular-component-of-saponin-adjuvants\/"},"modified":"2025-03-13T21:41:25","modified_gmt":"2025-03-14T00:41:25","slug":"identification-of-qs-21-as-an-inflammasome-activating-molecular-component-of-saponin-adjuvants","status":"publish","type":"post","link":"https:\/\/desertking.com\/es\/identification-of-qs-21-as-an-inflammasome-activating-molecular-component-of-saponin-adjuvants\/","title":{"rendered":"Identification of QS-21 as an Inflammasome-activating Molecular Component of Saponin Adjuvants"},"content":{"rendered":"<p><strong>Robyn Marty-Roix, Gregory I. Vladimer, Kimberly Pouliot, Dan Weng, Rachel Buglione-Corbett, Kim West,John D. MacMicking, Jonathan D. Chee, Shixia Wang, Shan Lu, and Egil Lien<\/strong><\/p>\n<p>Many immunostimulants act as vaccine adjuvants via activa- tion of the innate immune system, although in many cases it is unclear which specific molecules contribute to the stimulatory activity. QS-21 is a defined, highly purified, and soluble saponin adjuvant currently used in licensed and exploratory vaccines, including vaccines against malaria, cancer, and HIV-1. How- ever, little is known about the mechanisms of cellular activation induced by QS-21. We observed QS-21 to elicit caspase-1-de- pendent IL-1 and IL-18 release in antigen-presenting cells such as macrophages and dendritic cells when co-stimulated with the TLR4-agonist adjuvant monophosphoryl lipid A. Fur- thermore, our data suggest that the ASC-NLRP3 inflammasome is responsible for QS-21-induced IL-1 \/IL-18 release. At higher concentrations, QS-21 induced macrophage and dendritic cell death in a caspase-1-, ASC-, and NLRP3-independent manner, whereas the presence of cholesterol rescued cell viability. A nanoparticulate adjuvant that contains QS-21 as part of a heter- ogeneous mixture of saponins also induced IL-1 in an NLRP3- dependent manner. Interestingly, despite the role NLRP3 plays for cellular activation in vitro, NLRP3-deficient mice immu- nized with HIV-1 gp120 and QS-21 showed significantly higher levels of Th1 and Th2 antigen-specific T cell responses and increased IgG1 and IgG2c compared with wild type controls. Thus, we have identified QS-21 as a nonparticulate single molecular saponin that activates the NLRP3 inflammasome, but this signaling pathway may contribute to decreased antigen- specific responses in vivo.<\/p>\n<a href=\"https:\/\/desertking.com\/wp-content\/uploads\/2016\/09\/MartyRoixEtAl2016-IdentificationQs21AsInflammasomeActivatingMolecularCom....pdf\" class=\"pdfemb-viewer\" style=\"\" data-width=\"max\" data-height=\"max\" data-toolbar=\"bottom\" data-toolbar-fixed=\"off\">MartyRoixEtAl2016-IdentificationQs21AsInflammasomeActivatingMolecularCom...<\/a>\n","protected":false},"excerpt":{"rendered":"<p>Robyn Marty-Roix, Gregory I. Vladimer, Kimberly Pouliot, Dan Weng, Rachel Buglione-Corbett, Kim West,John D. MacMicking, Jonathan D. Chee, Shixia Wang, Shan Lu, and Egil Lien Many immunostimulants act as vaccine adjuvants via activa- tion of the innate immune system, although in many cases it is unclear which specific molecules contribute to the stimulatory activity. QS-21 [&hellip;]<\/p>\n","protected":false},"author":16,"featured_media":2216,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"rs_blank_template":"","rs_page_bg_color":"","slide_template_v7":"","footnotes":""},"categories":[9],"tags":[],"class_list":["post-1315","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/posts\/1315","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/users\/16"}],"replies":[{"embeddable":true,"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/comments?post=1315"}],"version-history":[{"count":0,"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/posts\/1315\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/media\/2216"}],"wp:attachment":[{"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/media?parent=1315"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/categories?post=1315"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/desertking.com\/es\/wp-json\/wp\/v2\/tags?post=1315"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}