{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:47:57Z","timestamp":1792622877412,"version":"4.5.0"},"reference-count":55,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,10,2]]},"abstract":"<jats:p>The enterobacterial pathogen Salmonella induces phagocyte apoptosis in vitro and in vivo. These bacteria use a specialized type III secretion system to export a virulence factor, SipB, which directly activates the host's apoptotic machinery by targeting caspase-1. Caspase-1 is not involved in most apoptotic processes but plays a major role in cytokine maturation. We show that caspase-1\u2013deficient macrophages undergo apoptosis within 4\u20136 h of infection with invasive bacteria. This process requires SipB, implying that this protein can initiate the apoptotic machinery by regulating components distinct from caspase-1. Invasive Salmonella typhimurium targets caspase-2 simultaneously with, but independently of, caspase-1. Besides caspase-2, the caspase-1\u2013independent pathway involves the activation of caspase-3, -6, and -8 and the release of cytochrome c from mitochondria, none of which occurs during caspase-1\u2013dependent apoptosis. By using caspase-2 knockout macrophages and chemical inhibition, we establish a role for caspase-2 in both caspase-1\u2013dependent and \u2013independent apoptosis. Particularly, activation of caspase-1 during fast Salmonella-induced apoptosis partially relies on caspase-2. The ability of Salmonella to induce caspase-1\u2013independent macrophage apoptosis may play a role in situations in which activation of this protease is either prevented or uncoupled from the induction of apoptosis.<\/jats:p>","DOI":"10.1084\/jem.192.7.1035","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1035-1046","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":149,"title":["<i>Salmonella<\/i>-Induced Caspase-2 Activation in Macrophages"],"prefix":"10.1084","volume":"192","author":[{"given":"Veronika","family":"Jesenberger","sequence":"first","affiliation":[{"name":"aDepartment of Cell- and Microbiology, Institute of Microbiology and Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna J.","family":"Procyk","sequence":"additional","affiliation":[{"name":"aDepartment of Cell- and Microbiology, Institute of Microbiology and Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Yuan","sequence":"additional","affiliation":[{"name":"cDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Reipert","sequence":"additional","affiliation":[{"name":"bDepartment of Molecular Cell Biology, Institute of Biochemistry and Molecular Cell Biology, Vienna Biocenter, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Baccarini","sequence":"additional","affiliation":[{"name":"aDepartment of Cell- and Microbiology, Institute of Microbiology and Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,10,2]]},"reference":[{"key":"2023072509293725900_R1","doi-asserted-by":"crossref","first-page":"R277","DOI":"10.1016\/S0960-9822(99)80178-X","article-title":"Bacterial invasionforce feeding by Salmonella","volume":"9","author":"Brumell","year":"1999","journal-title":"Curr. 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