Immunology Institute and Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Nat Rev Immunol. 2014 Sep;14(9):601-18. doi: 10.1038/nri3720.
Historically, cell death and inflammation have been closely linked, but the necessary divergence of the fields in the past few decades has enriched our molecular understanding of the signalling pathways that mediate various programmes of cell death and multiple types of inflammatory responses. The fields have now come together again demonstrating a surprising level of integration. Intimate interconnections at multiple levels are revealed between the cell death and inflammatory signal transduction pathways that are mobilized in response to the engagement of pattern recognition receptors during microbial infection. Molecules such as receptor-interacting protein kinase 1 (RIPK1), RIPK3, FAS-associated death domain protein (FADD), FLICE-like inhibitory protein (FLIP) and caspase 8 - which are associated with different forms of cell death - are incorporated into compatible and exceedingly dynamic Toll-like receptor, NOD-like receptor and RIG-I-like receptor signalling modules. These signalling modules have a high capacity to switch from inflammation to cell death, or a programmed execution of both, all in an orchestrated battle for host defence and survival.
从历史上看，细胞死亡和炎症一直密切相关，但过去几十年中这两个领域的必要分歧丰富了我们对介导各种细胞死亡程序和多种炎症反应的信号通路的分子理解。现在这两个领域又重新结合在一起，显示出惊人的整合水平。在微生物感染过程中，模式识别受体被激活，细胞死亡和炎症信号转导途径被动员起来，两者之间在多个层次上揭示了密切的相互联系。与不同形式的细胞死亡相关的分子，如受体相互作用蛋白激酶 1（RIPK1）、RIPK3、FAS 相关死亡结构域蛋白（FADD）、FLICE 样抑制蛋白（FLIP）和半胱天冬酶 8，被纳入兼容且极其动态的 Toll 样受体、NOD 样受体和 RIG-I 样受体信号模块。这些信号模块具有从炎症向细胞死亡转换，或两者同时程序化执行的高能力，所有这些都是为了宿主防御和生存的协调战斗。
