Membrane Damage during Listeria monocytogenes Infection Triggers a Caspase-7 Dependent Cytoprotective Response

PLoS Pathogens

Thirumala Devi Kanneganti¹  Sara K. B. Cassidy²  Jon A. Hagar²  Mary X. D. O'Riordan²  Luigi Franchi³  Gabriel Nuñez³ 

[1] Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America;Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America;Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, United States of America

关键词: Listeria monocytogenes;    Cell membranes;    Toxins;    Macrophages;    Apoptosis;    Intracellular pathogens;    Host cells;    Immunoblotting;   

DOI  :  10.1371/journal.ppat.1002628

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY