{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:09:26Z","timestamp":1791036566922,"version":"4.1.0"},"reference-count":57,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,7,17]]},"abstract":"<jats:p>Salmonella typhimurium invades host macrophages and induces apoptosis and the release of mature proinflammatory cytokines. SipB, a protein translocated by Salmonella into the cytoplasm of macrophages, is required for activation of Caspase-1 (Casp-1, an interleukin [IL]-1\u03b2\u2013converting enzyme), which is a member of a family of cysteine proteases that induce apoptosis in mammalian cells. Casp-1 is unique among caspases because it also directly cleaves the proinflammatory cytokines IL-1\u03b2 and IL-18 to produce bioactive cytokines. We show here that mice lacking Casp-1 (casp-1\u2212\/\u2212 mice) had an oral S. typhimurium 50% lethal dose (LD50) that was 1,000-fold higher than that of wild-type mice. Salmonella breached the M cell barrier of casp-1\u2212\/\u2212 mice efficiently; however, there was a decrease in the number of apoptotic cells, intracellular bacteria, and the recruitment of polymorphonuclear lymphocytes in the Peyer's patches (PP) as compared with wild-type mice. Furthermore, Salmonella did not disseminate systemically in the majority of casp-1\u2212\/\u2212 mice, as demonstrated by significantly less colonization in the PP, mesenteric lymph nodes, and spleens of casp-1\u2212\/\u2212 mice after an oral dose of S. typhimurium that was 100-fold higher than the LD50. The increased resistance in casp-1\u2212\/\u2212 animals appears specific for Salmonella infection since these mice were susceptible to colonization by another enteric pathogen, Yersinia pseudotuberculosis, which normally invades the PP. These results show that Casp-1, which is both proapoptotic and proinflammatory, is essential for S. typhimurium to efficiently colonize the cecum and PP and subsequently cause systemic typhoid-like disease in mice.<\/jats:p>","DOI":"10.1084\/jem.192.2.249","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"249-258","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":194,"title":["<i>Salmonella<\/i> Exploits Caspase-1 to Colonize Peyer's Patches in a Murine Typhoid Model"],"prefix":"10.1084","volume":"192","author":[{"given":"Denise M.","family":"Monack","sequence":"first","affiliation":[{"name":"aDepartment of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hersh","sequence":"additional","affiliation":[{"name":"cSkirball Institute, Department of Microbiology and Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nafisa","family":"Ghori","sequence":"additional","affiliation":[{"name":"aDepartment of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Bouley","sequence":"additional","affiliation":[{"name":"bDepartment of Comparative Medicine, Stanford School of Medicine, Stanford University, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Zychlinsky","sequence":"additional","affiliation":[{"name":"cSkirball Institute, Department of Microbiology and Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Falkow","sequence":"additional","affiliation":[{"name":"aDepartment of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,7,17]]},"reference":[{"key":"2023072509265091500_R1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1128\/CMR.12.3.405","article-title":"Molecular basis of the interaction of Salmonella with the intestinal mucosa","volume":"12","author":"Darwin","year":"1999","journal-title":"Clin. 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