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

Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity. Curr Opin Immunol. 2015 Jan 23;32C:78-83 Authors: Yang J, Zhao Y, Shao F 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 [PubMed - as supplied by publisher]
Source: Current Opinion in Immunology - Category: Allergy & Immunology Authors: Tags: Curr Opin Immunol Source Type: research