Chavarría-Smith Joseph, Vance Russell E
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Immunol Rev. 2015 May;265(1):22-34. doi: 10.1111/imr.12283.
Inflammasomes are cytosolic protein complexes that serve as platforms for the recruitment and activation of the pro-inflammatory CASPASE-1 protease. CASPASE-1 activation leads to processing and maturation of the cytokines interleukin-1β and interleukin-18 and a lytic form of cell death termed pyroptosis. Inflammasome assembly is initiated by cytosolic sensors in response to microbial infections. Many of these sensors, including NLRP1 (NLR family, pyrin domain containing 1), are described to form an inflammasome, but until recently, the mechanism of inflammasome activation and its physiological functions in host defense have remained unclear. In the last few years, important advances in our understanding of NLRP1 biology have been achieved. In this review, we discuss the activation of NLRP1 by various stimuli, including Bacillus anthracis lethal toxin, Toxoplasma gondii, muramyl dipeptide, and host intracellular ATP depletion. The role NLRP1 plays in pathogen recognition and resistance during infection is also discussed, as is the regulation of NLRP1 by host and viral proteins. We conclude by discussing the unexpected differences in the mechanism of NLRP1 inflammasome activation, as compared to the activation of other inflammasomes, such as the NAIP (NLR family, apoptosis inhibitory protein)/NLRC4 inflammasomes.
炎性小体是一种胞质蛋白复合物，作为募集和激活促炎性半胱天冬酶-1蛋白酶的平台。半胱天冬酶-1的激活导致细胞因子白细胞介素-1β和白细胞介素-18的加工和成熟，以及一种称为细胞焦亡的溶细胞性细胞死亡形式。炎性小体的组装由胞质传感器响应微生物感染而启动。这些传感器中的许多，包括NLRP1（含pyrin结构域的NLR家族成员1），被描述为可形成炎性小体，但直到最近，炎性小体激活的机制及其在宿主防御中的生理功能仍不清楚。在过去几年中，我们对NLRP1生物学的理解取得了重要进展。在这篇综述中，我们讨论了NLRP1被各种刺激激活的情况，包括炭疽杆菌致死毒素、弓形虫、胞壁酰二肽和宿主细胞内ATP耗竭。还讨论了NLRP1在感染期间病原体识别和抗性中所起的作用，以及宿主和病毒蛋白对NLRP1的调节。我们通过讨论NLRP1炎性小体激活机制与其他炎性小体（如NAIP（含凋亡抑制蛋白的NLR家族成员）/NLRC4炎性小体）激活机制的意外差异来结束本文。
