The <scp>NAIP</scp>–<scp>NLRC</scp>4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus

Abstract

Summary Bacterial flagella and type III secretion system (T3 SS ) are evolutionarily related molecular transport machineries. Flagella mediate bacterial motility; the T3 SS delivers virulence effectors to block host defenses. The inflammasome is a cytosolic multi‐protein complex that activates caspase‐1. Active caspase‐1 triggers interleukin‐1β ( IL ‐1β)/ 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 10 years have established a NAIP – NLRC 4 inflammasome, in which NAIP s are cytosolic receptors for bacterial flagellin and T3 SS rod/needle proteins, while NLRC 4 acts as an adapter for caspase‐1 activation. Given the wide presence of flagella and the T3 SS in bacteria, the NAIP – NLRC 4 inflammasome plays a critical role in anti‐bacteria defenses. Here, we review the discovery of the NAIP – NLRC 4 inflammasome and further discuss recent advances related to its biochemical mechanism and biological function as well as its connection to human autoinflammatory disease.

Keywords

Affiliated Institutions

• National Institute of Biological Sciences, Beijing CN

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