{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:26:34Z","timestamp":1789590394466,"version":"build-2803163510"},"reference-count":93,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"71","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,5,27]]},"abstract":"<jats:p>\n                    <jats:italic>Clostridium<\/jats:italic>\n                    species are a group of Gram-positive bacteria that cause diseases in humans, such as food poisoning, botulism, and tetanus. Here, we analyzed 10 different\n                    <jats:italic>Clostridium<\/jats:italic>\n                    species and identified that\n                    <jats:italic>Clostridium septicum<\/jats:italic>\n                    , a pathogen that causes sepsis and gas gangrene, activates the mammalian cytosolic inflammasome complex in mice and humans. Mechanistically, we demonstrate that \u03b1-toxin secreted by\n                    <jats:italic>C. septicum<\/jats:italic>\n                    binds to glycosylphosphatidylinositol (GPI)\u2013anchored proteins on the host plasma membrane, oligomerizing and forming a membrane pore that is permissive to efflux of magnesium and potassium ions. Efflux of these cytosolic ions triggers the activation of the innate immune sensor NLRP3, inducing activation of caspase-1 and gasdermin D, secretion of the proinflammatory cytokines interleukin-1\u03b2 and interleukin-18, pyroptosis, and plasma membrane rupture via ninjurin-1. Furthermore, \u03b1-toxin of\n                    <jats:italic>C. septicum<\/jats:italic>\n                    induces rapid inflammasome-mediated lethality in mice and pharmacological inhibition of the NLRP3 inflammasome using MCC950 prevents\n                    <jats:italic>C. septicum<\/jats:italic>\n                    \u2013induced lethality. Overall, our results reveal that cytosolic innate sensing of \u03b1-toxin is central to the recognition of\n                    <jats:italic>C. septicum<\/jats:italic>\n                    infection and that therapeutic blockade of the inflammasome pathway may prevent sepsis and death caused by toxin-producing pathogens.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.abm1803","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T13:57:15Z","timestamp":1653055035000},"source":"Crossref","is-referenced-by-count":45,"title":["<i>Clostridium septicum<\/i>\n                    \u03b1-toxin activates the NLRP3 inflammasome by engaging GPI-anchored proteins"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6747-6076","authenticated-orcid":true,"given":"Weidong","family":"Jing","sequence":"first","affiliation":[{"name":"Division of Immunity, Inflammation and Infection, The John Curtin School of Medical Research, The 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