Journal
IMMUNOLOGICAL REVIEWS
Volume 265, Issue 1, Pages 85-102Publisher
WILEY
DOI: 10.1111/imr.12293
Keywords
pattern recognition; innate immunity; NOD-like receptor; NLRs; inflammasome; flagellin
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Funding
- International Early Career Scientist grant from the Howard Hughes Medical Institute
- Beijing Scholar Program
- National Basic Research Program of China 973 Programs [2012CB518700, 2014CB849602]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB08020202]
- China National Science Foundation Program for Distinguished Young Scholars [31225002]
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Bacterial flagella and type III secretion system (T3SS) are evolutionarily related molecular transport machineries. Flagella mediate bacterial motility; the T3SS delivers virulence effectors to block host defenses. The inflammasome is a cytosolic multi-protein complex that activates caspase-1. Active caspase-1 triggers interleukin-1 (IL-1)/IL-18 maturation and macrophage pyroptotic death to mount an inflammatory response. Central to the inflammasome is a pattern recognition receptor that activates caspase-1 either directly or through an adapter protein. Studies in the past 10years have established a NAIP-NLRC4 inflammasome, in which NAIPs are cytosolic receptors for bacterial flagellin and T3SS rod/needle proteins, while NLRC4 acts as an adapter for caspase-1 activation. Given the wide presence of flagella and the T3SS in bacteria, the NAIP-NLRC4 inflammasome plays a critical role in anti-bacteria defenses. Here, we review the discovery of the NAIP-NLRC4 inflammasome and further discuss recent advances related to its biochemical mechanism and biological function as well as its connection to human autoinflammatory disease.
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