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

<jats:title>Summary</jats:title><jats:p>Bacterial flagella and type <jats:styled-content style="fixed-case">III</jats:styled-content> secretion system (T3<jats:styled-content style="fixed-case">SS</jats:styled-content>) are evolutionarily related molecular transport machineries. Flagella mediate bacterial motility; the T3<jats:styled-content style="fixed-case">SS</jats:styled-content> 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 (<jats:styled-content style="fixed-case">IL</jats:styled-content>‐1β)/<jats:styled-content style="fixed-case">IL</jats:styled-content>‐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 <jats:styled-content style="fixed-case">NAIP</jats:styled-content>–<jats:styled-content style="fixed-case">NLRC</jats:styled-content>4 inflammasome, in which <jats:styled-content style="fixed-case">NAIP</jats:styled-content>s are cytosolic receptors for bacterial flagellin and T3<jats:styled-content style="fixed-case">SS</jats:styled-content> rod/needle proteins, while <jats:styled-content style="fixed-case">NLRC</jats:styled-content>4 acts as an adapter for caspase‐1 activation. Given the wide presence of flagella and the T3<jats:styled-content style="fixed-case">SS</jats:styled-content> in bacteria, the <jats:styled-content style="fixed-case">NAIP</jats:styled-content>–<jats:styled-content style="fixed-case">NLRC</jats:styled-content>4 inflammasome plays a critical role in anti‐bacteria defenses. Here, we review the discovery of the <jats:styled-content style="fixed-case">NAIP</jats:styled-content>–<jats:styled-content style="fixed-case">NLRC</jats:styled-content>4 inflammasome and further discuss recent advances related to its biochemical mechanism and biological function as well as its connection to human autoinflammatory disease.</jats:p>