Shigella-induced apoptosis is dependent on Caspase-1 which binds to IpaB

We report here that the Shigella invasion plasmid antigen (Ipa)B, which is sufficient to induce apoptosis in macrophages, binds to caspase (Casp)-1, b ut not to Casp-8 or Casp-3, Casp-1 is activated and its specific substrate interleukin-1 beta is cleaved shortly after Shigella infection. Macrophages isolated from Casp-1 knockout mice are not susceptible to Shigella-induced apoptosis, although they respond normally to other apoptotic stimuli. Shig ella kills macrophages from casp-3, casp-11, and p53 knock-out mice as well as macrophages overexpressing Bcl-2, We propose that Shigella induces apop tosis by directly activating Casp-1 through IpaB, bypassing signal transduc tion events and caspases upstream of Casp-1. Taken together these data indi cate that Shigella-induced apoptosis is distinct from other forms of apopto sis and seems uniquely dependent on Casp-1.