@article{JesenbergerProcykYuanetal.,
  author    = {Jesenberger, Veronika and Procyk, Katarzyna and Yuan, Junying and Reipert, Siegfried and Baccarini, Manuela},
  title     = {Salmonella-induced caspase-2 activation in macrophages: a novel mechanism in pathogen-mediated apoptosis},
  series = {J Exp Med.},
  volume    = {2000},
  journal   = {J Exp Med.},
  number    = {192(7)},
  doi       = {10.1084/jem.192.7.1035},
  pages     = {1035 -- 1046},
  abstract  = {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-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 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.},
  subject      = {caspase-2 activation in macrophages},
  language  = {en}
}