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, but not to Casp-2 or Casp-3. Casp-1 is activated and its specific substrate interleukin-1beta is cleaved shortly after Shigella infection. Macrophages isolated from Casp-1 knock-out mice are not susceptible to Shigella-induced apoptosis, although they respond normally to other apoptotic stimuli. Shigella kills macrophages from casp-3, casp-11, and p53 knock-out mice as well as macrophages overexpressing Bcl-2. We propose that Shigella induces apoptosis by directly activating Casp-1 through IpaB, bypassing signal transduction events and caspases upstream of Casp-1. Taken together these data indicate that Shigella-induced apoptosis is distinct from other forms of apoptosis and seems uniquely dependent on Casp-1.
Hilbi
H
H
Skirball Institute, Department of Microbiology and Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
Moss
J E
JE
Hersh
D
D
Chen
Y
Y
Arondel
J
J
Banerjee
S
S
Flavell
R A
RA
Yuan
J
J
Sansonetti
P J
PJ
Zychlinsky
A
A
D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D012760:Shigella / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D001426:Bacterial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C087447:ipaB protein, Shigella; D020170:Caspase 1