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Science 339 (6122): 975-978

Copyright © 2013 by the American Association for the Advancement of Science

Caspase-11 Protects Against Bacteria That Escape the Vacuole

Youssef Aachoui,1,2,{dagger} Irina A. Leaf,3,{dagger} Jon A. Hagar,1,2,{dagger} Mary F. Fontana,4,* Cristine G. Campos,1 Daniel E. Zak,3 Michael H. Tan,4 Peggy A. Cotter,1 Russell E. Vance,4 Alan Aderem,3 Edward A. Miao1,2,{ddagger}

Abstract: Caspases are either apoptotic or inflammatory. Among inflammatory caspases, caspase-1 and -11 trigger pyroptosis, a form of programmed cell death. Whereas both can be detrimental in inflammatory disease, only caspase-1 has an established protective role during infection. Here, we report that caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria. Although Salmonella typhimurium and Legionella pneumophila normally reside in the vacuole, specific mutants (sifA and sdhA, respectively) aberrantly enter the cytosol. These mutants triggered caspase-11, which enhanced clearance of S. typhimurium sifA in vivo. This response did not require NLRP3, NLRC4, or ASC inflammasome pathways. Burkholderia species that naturally invade the cytosol also triggered caspase-11, which protected mice from lethal challenge with B. thailandensis and B. pseudomallei. Thus, caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens.

1 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
2 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
3 Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
4 Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720, USA.

* Present address: Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA 94122, USA.

{dagger} These authors contributed equally to this manuscript.

{ddagger} To whom correspondence should be addressed. E-mail: emiao{at}med.unc.edu


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