Department of Medicine, Radboud University Nijmegen Medical Center, and Nijmegen Center for Infections, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
PLoS Pathog. 2010 Feb 26;6(2):e1000661. doi: 10.1371/journal.ppat.1000661.
Stimulation and release of proinflammatory cytokines is an essential step for the activation of an effective innate host defense, and subsequently for the modulation of adaptive immune responses. Interleukin-1beta (IL-1beta) and IL-18 are important proinflammatory cytokines that on the one hand activate monocytes, macropages, and neutrophils, and on the other hand induce Th1 and Th17 adaptive cellular responses. They are secreted as inactive precursors, and the processing of pro-IL-1beta and pro-IL-18 depends on cleavage by proteases. One of the most important of these enzymes is caspase-1, which in turn is activated by several protein platforms called the inflammasomes. Inflammasome activation differs in various cell types, and knock-out mice defective in either caspase-1 or inflammasome components have an increased susceptibility to several types of infections. However, in other infections and in models of sterile inflammation, caspase-1 seems to be less important, and alternative mechanisms such as neutrophil-derived serine proteases or proteases released from microbial pathogens can process and activate IL-1beta. In conclusion, IL-1beta/IL-18 processing during infection is a complex process in which the inflammasomes are only one of several activation mechanisms.
刺激和释放促炎细胞因子是激活有效的先天宿主防御的关键步骤，随后还能调节适应性免疫反应。白细胞介素-1β（IL-1β）和 IL-18 是重要的促炎细胞因子，一方面激活单核细胞、巨噬细胞和中性粒细胞，另一方面诱导 Th1 和 Th17 适应性细胞反应。它们以无活性前体的形式分泌，而 pro-IL-1β 和 pro-IL-18 的加工取决于蛋白酶的切割。其中最重要的酶之一是半胱天冬酶-1，它反过来又被几种称为炎性体的蛋白质平台激活。炎性体的激活在不同的细胞类型中有所不同，缺乏半胱天冬酶-1 或炎性体成分的敲除小鼠对几种类型的感染更敏感。然而，在其他感染和无菌性炎症模型中，半胱天冬酶-1 似乎不那么重要，中性粒细胞衍生的丝氨酸蛋白酶或来自微生物病原体的蛋白酶等替代机制可以加工和激活 IL-1β。总之，感染过程中 IL-1β/IL-18 的加工是一个复杂的过程，其中炎性体只是几种激活机制之一。
