Caspase-11 protects against bacteria that escape the vacuole.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Aachoui, Y; Leaf, IA; Hagar, JA; Fontana, MF; Campos, CG; Zak, DE; Tan, MH; Cotter, PA; Vance, RE; Aderem, A; Miao, EA

Published Date

  • February 2013

Published In

Volume / Issue

  • 339 / 6122

Start / End Page

  • 975 - 978

PubMed ID

  • 23348507

Pubmed Central ID

  • 23348507

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1230751

Language

  • eng