The NAIP-NLRC4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus

• Published in: Immunological reviews Vol. 265; no. 1; pp. 85 - 102
• Main Authors: Zhao, Yue, Shao, Feng
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2015
• Subjects: Animals; Bacterial Infections - immunology; Bacterial Proteins - metabolism; Calcium-Binding Proteins - metabolism; CARD Signaling Adaptor Proteins - metabolism; flagellin; Flagellin - metabolism; Humans; Immunity, Innate; inflammasome; Inflammasomes - immunology; Inflammasomes - metabolism; innate immunity; Neuronal Apoptosis-Inhibitory Protein - metabolism; NLRs; NOD-like receptor; pattern recognition; Type III Secretion Systems - metabolism; NOD-like receptor; flagellin; NLRs; innate immunity; inflammasome; pattern recognition
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.12293

Summary 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‐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–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.