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dc.contributor.authorJesenberger, Veronika
dc.contributor.authorProcyk, Katarzyna J.
dc.contributor.authorYuan, Junying
dc.contributor.authorReipert, Siegfried
dc.contributor.authorBaccarini, Manuela
dc.date.accessioned2019-10-05T16:05:14Z
dc.date.issued2000
dc.identifier.citationJesenberger, Veronika, Katarzyna J. Procyk, Junying Yuan, Siegfried Reipert, and Manuela Baccarini. 2000. “Salmonella-Induced Caspase-2 Activation in Macrophages.” The Journal of Experimental Medicine 192 (7): 1035–46. https://doi.org/10.1084/jem.192.7.1035.
dc.identifier.issn0022-1007
dc.identifier.issn1540-9538
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483505*
dc.description.abstractThe 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-deficient macrophages undergo apoptosis within 4-6 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-independent pathway involves the activation of caspase-3, -6, and -8 and the release of cytochrome c from mitochondria, none of a which occurs during caspase-1-dependent apoptosis. By using caspase-2 knockout macrophages and chemical inhibition, we establish a role for caspase-2 in both caspase-1-dependent and -independent apoptosis. Particularly, activation of caspase-1 during fast Salmonella-induced apoptosis partially relies on caspase-2. The ability of Salmonella to induce caspase-1-independent macrophage apoptosis may play a role in situations in which activation of this protease is either prevented or uncoupled from the induction of apoptosis.
dc.language.isoen_US
dc.publisherRockefeller University Press
dash.licenseLAA
dc.titleSalmonella-Induced Caspase-2 Activation in Macrophages a Novel Mechanism in Pathogen-Mediated Apoptosis
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalThe Journal of Experimental Medicine
dash.depositing.authorYuan, Junying::c7e832b918fc7c2356d6c49fe1a0b135::600
dc.date.available2019-10-05T16:05:14Z
dash.workflow.comments1Science Serial ID 108474
dc.identifier.doi10.1084/jem.192.7.1035
dash.source.volume192;7
dash.source.page1035-10346


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