title: The NAIP-NLRC4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus.
abstract: 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.
authors: National Institute of Biological Sciences, Beijing, China.
authors: Yue
authors: Y
authors: Zhao
authors: Feng
authors: F
authors: Shao
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D001426:Bacterial Proteins / Q000378:metabolism*; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D005408:Flagellin / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000378:metabolism*; D000069296:Type III Secretion Systems / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D058847:Inflammasomes; C435692:NLRC4 protein, human; D051616:Neuronal Apoptosis-Inhibitory Protein; D000069296:Type III Secretion Systems; D005408:Flagellin
keywords: NLRs; NOD-like receptor; flagellin; inflammasome; innate immunity; pattern recognition