Zhao Yue, Shao Feng
National Institute of Biological Sciences, Beijing, China.
Immunol Rev. 2015 May;265(1):85-102. doi: 10.1111/imr.12293.
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.
细菌鞭毛和III型分泌系统（T3SS）是在进化上相关的分子转运机制。鞭毛介导细菌的运动性；T3SS将毒力效应蛋白传递至宿主以阻断宿主防御。炎性小体是一种激活半胱天冬酶-1的胞质多蛋白复合物。活性半胱天冬酶-1触发白细胞介素-1β（IL-1β）/IL-18的成熟以及巨噬细胞焦亡性死亡，从而引发炎症反应。炎性小体的核心是一种模式识别受体，它可直接或通过衔接蛋白激活半胱天冬酶-1。过去10年的研究确立了NAIP-NLRC4炎性小体，其中NAIPs是细菌鞭毛蛋白和T3SS杆状/针状蛋白的胞质受体，而NLRC4作为激活半胱天冬酶-1的衔接蛋白。鉴于鞭毛和T3SS在细菌中广泛存在，NAIP-NLRC4炎性小体在抗菌防御中发挥着关键作用。在此，我们回顾NAIP-NLRC4炎性小体的发现，并进一步讨论与其生化机制、生物学功能以及与人类自身炎症性疾病的关联相关的最新进展。
