Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock.

Journal Article (Journal Article)

Inflammatory caspases, such as caspase-1 and -11, mediate innate immune detection of pathogens. Caspase-11 induces pyroptosis, a form of programmed cell death, and specifically defends against bacterial pathogens that invade the cytosol. During endotoxemia, however, excessive caspase-11 activation causes shock. We report that contamination of the cytoplasm by lipopolysaccharide (LPS) is the signal that triggers caspase-11 activation in mice. Specifically, caspase-11 responds to penta- and hexa-acylated lipid A, whereas tetra-acylated lipid A is not detected, providing a mechanism of evasion for cytosol-invasive Francisella. Priming the caspase-11 pathway in vivo resulted in extreme sensitivity to subsequent LPS challenge in both wild-type and Tlr4-deficient mice, whereas Casp11-deficient mice were relatively resistant. Together, our data reveal a new pathway for detecting cytoplasmic LPS.

Full Text

Duke Authors

Cited Authors

  • Hagar, JA; Powell, DA; Aachoui, Y; Ernst, RK; Miao, EA

Published Date

  • September 13, 2013

Published In

Volume / Issue

  • 341 / 6151

Start / End Page

  • 1250 - 1253

PubMed ID

  • 24031018

Pubmed Central ID

  • PMC3931427

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1240988


  • eng

Conference Location

  • United States