Format

Send to

Choose Destination
Curr Opin Immunol. 2015 Feb;32:78-83. doi: 10.1016/j.coi.2015.01.007. Epub 2015 Jan 24.

Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity.

Author information

1
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; National Institute of Biological Sciences, Beijing 102206, China.
2
National Institute of Biological Sciences, Beijing 102206, China.
3
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; National Institute of Biological Sciences, Beijing 102206, China. Electronic address: shaofeng@nibs.ac.cn.

Abstract

Lipopolysaccharide (LPS) is the major component of Gram-negative bacteria cell wall. In innate immunity, extracellular LPS is recognized by Toll-like receptor 4 to stimulate cytokine transcription. Recent studies suggest a 'non-canonical inflammasome' that senses cytoplasmic LPS and activates caspase-11 in mouse macrophages. Unexpectedly, biochemical studies reveal that caspase-11 and its human orthologs caspase-4/caspase-5 are LPS receptors themselves. Direct LPS binding induces caspase-4/caspase-5/caspase-11 oligomerization and activation, triggering cell pyroptosis and anti-bacterial defenses. Caspase-4/caspase-5/caspase-11 recognition of intracellular LPS requires bacterial escape from the vacuole; this process is promoted by interferon-inducible GTPases-mediated lysis of the bacteria-containing vacuole. Non-canonical activation of these inflammatory caspases by LPS not only represents a new paradigm in innate immunity but also critically determines LPS-induced septic shock in mice.

PMID:
25621708
DOI:
10.1016/j.coi.2015.01.007
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center