Yeretssian Garabet, Labbé Katherine, Saleh Maya
Department of Medicine, Division of Critical Care, and Centre for the Study of Host Resistance, McGill University, Montreal, Que., Canada.
Cytokine. 2008 Sep;43(3):380-90. doi: 10.1016/j.cyto.2008.07.015. Epub 2008 Aug 13.
Cell death and innate immunity are ancient evolutionary conserved processes that utilize a dazzling number of related molecular effectors and parallel signal transduction mechanisms. The investigation of the molecular mechanisms linking the sensing of a danger signal (pathogens or tissue damage) to the induction of an inflammatory response has witnessed a renaissance in the last few years. This was initiated by the identification of pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and more recently cytosolic Nod-like receptors (NLRs), that brought innate immunity to center stage and opened the field to the study of signal transduction pathways, adaptors and central effectors linked to PRRs. This led to the characterization of the inflammasome, a macromolecular complex, scaffolded by NLRs, that recruits and activates inflammatory caspases, which are essential effectors in inflammation and cell death responses. In this review, we describe the molecular pathways of cell death and innate immunity with a focus on recent advancements in both fields and an emphasis on the striking analogies between NLR innate immunity and mitochondrial apoptosis pathways.
细胞死亡和固有免疫是古老的、在进化上保守的过程，它们利用了大量相关的分子效应器和并行的信号转导机制。在过去几年中，对将危险信号（病原体或组织损伤）的感知与炎症反应的诱导联系起来的分子机制的研究经历了复兴。这一复兴始于模式识别受体（PRR）的发现，包括Toll样受体（TLR）以及最近发现的胞质Nod样受体（NLR），这些受体将固有免疫推到了舞台中央，并开启了对与PRR相关的信号转导途径、衔接蛋白和核心效应器的研究领域。这导致了炎性小体的表征，炎性小体是一种由NLR搭建的大分子复合物，它招募并激活炎性半胱天冬酶，而炎性半胱天冬酶是炎症和细胞死亡反应中的关键效应器。在这篇综述中，我们描述细胞死亡和固有免疫的分子途径，重点关注这两个领域的最新进展，并强调NLR固有免疫与线粒体凋亡途径之间惊人的相似之处。
