The NAIP–NLRC4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus
The NAIP–NLRC4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus
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DOI：
10.1111/imr.12293
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发表时间：
2015-05
影响因子：
8.7
通讯作者：
Yue Zhao;F. Shao
中科院分区：
文献类型：
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作者：
Yue Zhao;F. Shao
细菌鞭毛和III型分泌系统（T3SS）是进化相关的分子运输机制。鞭毛介导细菌运动；T3SS提供毒力效应物来阻断宿主防御。炎性小体是一种激活半胱天冬酶- 1的胞质多蛋白复合物。活性caspase‐1触发白细胞介素- 1β (IL‐1β)/IL‐18成熟和巨噬细胞热噬性死亡，引起炎症反应。炎症小体的核心是一种模式识别受体，可直接或通过一种适配蛋白激活caspase‐1。过去10年的研究已经建立了NAIP-NLRC4炎症小体，其中naip是细菌鞭毛蛋白和T3SS棒/针蛋白的细胞质受体，而NLRC4是caspase‐1激活的适配器。鉴于鞭毛和T3SS在细菌中的广泛存在，NAIP-NLRC4炎症小体在抗细菌防御中起着关键作用。在此，我们回顾了NAIP-NLRC4炎性小体的发现，并进一步讨论了其生化机制和生物学功能及其与人类自身炎症疾病的关系的最新进展。
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.