Membrane damage during Listeria monocytogenes infection triggers a caspase-7 dependent cytoprotective response

The cysteine protease caspase-7 has an established role in the execution of apoptotic cell death,but recent findings also suggest involvement of caspase-7 during the host response to microbial infection. caspase-7 can be cleaved by the inflammatory caspase,caspase-1,and has been implicated in processing and activation of microbial virulence factors. thus,caspase-7 function during microbial infection may be complex,and its role in infection and immunity has yet to be fully elucidated. here we demonstrate that caspase-7 is cleaved during cytosolic infection with the intracellular bacterial pathogen,listeria monocytogenes. cleavage of caspase-7 during l. monocytogenes infection did not require caspase-1 or key adaptors of the primary pathways of innate immune signaling in this infection,asc,rip2 and myd88. caspase-7 protected infected macrophages against plasma membrane damage attributable to the bacterial pore-forming toxin listeriolysin o (llo). llo-mediated membrane damage could itself trigger caspase-7 cleavage,independently of infection or overt cell death. we also detected caspase-7 cleavage upon treatment with other bacterial pore-forming toxins,but not in response to detergents. taken together,our results support a model where cleavage of caspase-7 is a consequence of toxin-mediated membrane damage,a common occurrence during infection. we propose that host activation of caspase-7 in response to pore formation represents an adaptive mechanism by which host cells can protect membrane integrity during infection. © 2012 cassidy et al.