Liu An-Nan, Sun Tie-Ying
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Sheng Li Xue Bao. 2012 Dec 25;64(6):741-50.
The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ-line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so-called pathogen-associated molecular patterns (PAMPs). A subset of PRRs, belonging to the nucleotide binding oligomerization domain (NOD)-like receptor (NLR) families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi-protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the cysteine protease Caspase-1, a central mediator of innate immunity. Caspase-1 initiates a novel form of cell death called pyroptosis. Inflammasome activation by pathogen-associated signatures results in the autocatalytic cleavage of Caspase-1 and ultimately leads to the processing and thus secretion of pro-inflammatory cytokines, most importantly interleukin (IL)-1β and IL-18. Here, we review the recent advancements of negative regulatory functions and mechanisms leading to the activation of NLRP1, NLRP3, NLRC4, and AIM2 inflammasomes.
固有免疫系统在快速识别和清除入侵微生物方面发挥着关键作用。微生物的检测依赖于种系编码的模式识别受体（PRR），这些受体能够识别重要的细菌分子，即所谓的病原体相关分子模式（PAMP）。PRR的一个子集属于核苷酸结合寡聚化结构域（NOD）样受体（NLR）家族，可在宿主细胞的胞质溶胶中检测病毒和细菌病原体，并诱导称为炎性小体的多蛋白信号平台的组装。炎性小体作为半胱氨酸蛋白酶Caspase-1的激活平台，Caspase-1是固有免疫的核心介质。Caspase-1引发一种称为细胞焦亡的新型细胞死亡形式。病原体相关信号激活炎性小体导致Caspase-1的自催化裂解，并最终导致促炎细胞因子的加工和分泌，最重要的是白细胞介素（IL）-1β和IL-18。在此，我们综述了导致NLRP1、NLRP3、NLRC4和AIM2炎性小体激活的负调控功能和机制的最新进展。
