Vance Russell E
Howard Hughes Medical Institute, United States; Department of Molecular and Cell Biology, United States; Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720, United States.
Curr Opin Immunol. 2015 Feb;32:84-9. doi: 10.1016/j.coi.2015.01.010. Epub 2015 Jan 24.
Inflammasomes comprise a family of cytosolic multi-protein complexes that sense infection, or other threats, and initiate inflammation via the recruitment and activation of the Caspase-1 protease. Although the precise molecular mechanism by which most inflammasomes are activated remains a subject of considerable debate, the NAIP/NLRC4 subfamily of inflammasomes is increasingly well understood. A crystal structure of NLRC4 was recently reported, and a domain in NAIPs that recognizes bacterial ligands was identified. In addition, gain-of-function mutations in NLRC4 have been shown to cause an auto-inflammatory syndrome in humans. Lastly, the NAIP/NLRC4 inflammasome has been shown to provide a novel form of cell intrinsic defense against Salmonella infection, involving expulsion of infected cells from the intestinal epithelium.
炎性小体是一类胞质多蛋白复合物家族,可感知感染或其他威胁,并通过募集和激活半胱天冬酶-1蛋白酶来引发炎症。尽管大多数炎性小体被激活的确切分子机制仍是一个备受争议的话题,但炎性小体的NAIP/NLRC4亚家族越来越为人所熟知。最近报道了NLRC4的晶体结构,并鉴定出NAIPs中识别细菌配体的一个结构域。此外,NLRC4中的功能获得性突变已被证明会导致人类自身炎症综合征。最后,NAIP/NLRC4炎性小体已被证明可提供一种针对沙门氏菌感染的新型细胞内源性防御形式,包括将感染细胞从肠道上皮中排出。