Martinon Fabio, Mayor Annick, Tschopp Jürg
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Annu Rev Immunol. 2009;27:229-65. doi: 10.1146/annurev.immunol.021908.132715.
The innate immune system relies on its capacity to rapidly detect invading pathogenic microbes as foreign and to eliminate them. The discovery of Toll-like receptors (TLRs) provided a class of membrane receptors that sense extracellular microbes and trigger antipathogen signaling cascades. More recently, intracellular microbial sensors have been identified, including NOD-like receptors (NLRs). Some of the NLRs also sense nonmicrobial danger signals and form large cytoplasmic complexes called inflammasomes that link the sensing of microbial products and metabolic stress to the proteolytic activation of the proinflammatory cytokines IL-1beta and IL-18. The NALP3 inflammasome has been associated with several autoinflammatory conditions including gout. Likewise, the NALP3 inflammasome is a crucial element in the adjuvant effect of aluminum and can direct a humoral adaptive immune response. In this review, we discuss the role of NLRs, and in particular the inflammasomes, in the recognition of microbial and danger components and the role they play in health and disease.
天然免疫系统依赖于其快速检测入侵的病原微生物为外来物并将其清除的能力。Toll样受体(TLR)的发现提供了一类可感知细胞外微生物并触发抗病原体信号级联反应的膜受体。最近,已鉴定出细胞内微生物传感器,包括NOD样受体(NLR)。一些NLR还可感知非微生物危险信号并形成称为炎性小体的大型细胞质复合物,该复合物将微生物产物和代谢应激的感知与促炎细胞因子IL-1β和IL-18的蛋白水解激活联系起来。NALP3炎性小体已与包括痛风在内的几种自身炎症性疾病相关。同样,NALP3炎性小体是铝佐剂效应的关键要素,并且可以指导体液适应性免疫反应。在本综述中,我们讨论了NLR,特别是炎性小体,在识别微生物和危险成分中的作用以及它们在健康和疾病中所起的作用。