| First Author | Cassidy SK | Year | 2012 |
| Journal | PLoS Pathog | Volume | 8 |
| Issue | 7 | Pages | e1002628 |
| PubMed ID | 22807671 | Mgi Jnum | J:195378 |
| Mgi Id | MGI:5478686 | Doi | 10.1371/journal.ppat.1002628 |
| Citation | Cassidy SK, et al. (2012) Membrane damage during Listeria monocytogenes infection triggers a caspase-7 dependent cytoprotective response. PLoS Pathog 8(7):e1002628 |
| abstractText | 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. |
