{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:56:13Z","timestamp":1791327373791,"version":"4.3.1"},"reference-count":22,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,10,17]]},"abstract":"<jats:p>Francisella tularensis is a highly infectious gram-negative coccobacillus that causes the zoonosis tularemia. This bacterial pathogen causes a plague-like disease in humans after exposure to as few as 10 cells. Many of the mechanisms by which the innate immune system fights Francisella are unknown. Here we show that wild-type Francisella, which reach the cytosol, but not Francisella mutants that remain localized to the vacuole, induced a host defense response in macrophages, which is dependent on caspase-1 and the death-fold containing adaptor protein ASC. Caspase-1 and ASC signaling resulted in host cell death and the release of the proinflammatory cytokines interleukin (IL)-1\u03b2 and IL-18. F. tularensis\u2013infected caspase-1\u2013 and ASC-deficient mice showed markedly increased bacterial burdens and mortality as compared with wild-type mice, demonstrating a key role for caspase-1 and ASC in innate defense against infection by this pathogen.<\/jats:p>","DOI":"10.1084\/jem.20050977","type":"journal-article","created":{"date-parts":[[2005,10,17]],"date-time":"2005-10-17T19:13:29Z","timestamp":1129576409000},"page":"1043-1049","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":344,"title":["Innate immunity against <i>Francisella tularensis<\/i> is dependent on the ASC\/caspase-1 axis"],"prefix":"10.1084","volume":"202","author":[{"given":"Sanjeev","family":"Mariathasan","sequence":"first","affiliation":[{"name":"1Molecular Oncology Department, Genentech Inc., South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Weiss","sequence":"additional","affiliation":[{"name":"2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishva M.","family":"Dixit","sequence":"additional","affiliation":[{"name":"1Molecular Oncology Department, Genentech Inc., South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise M.","family":"Monack","sequence":"additional","affiliation":[{"name":"2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,10,17]]},"reference":[{"key":"2023072513241975300_BIB1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S1369-5274(03)00002-X","volume":"6","year":"2003","journal-title":"Curr. 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