Biswas Subhra K, Lopez-Collazo Eduardo
Singapore Immunology Network, Biomedical Sciences Institutes, Agency for Science, Technology and Research, #04-01 Immunos, 8A Biomedical Drive, 138648 Singapore.
Trends Immunol. 2009 Oct;30(10):475-87. doi: 10.1016/j.it.2009.07.009. Epub 2009 Sep 24.
Prior exposure of innate immune cells like monocytes/macrophages to minute amounts of endotoxin cause them to become refractory to subsequent endotoxin challenge, a phenomenon called "endotoxin tolerance". Clinically, this state is associated with monocytes/macrophages in sepsis patients where they contribute to "immunosuppression" and mortality. The molecular mechanisms underlying endotoxin tolerance remain elusive. The recent appreciation of inflammation as a self-regulating process, the relative contribution of MyD88 versus TRIF signaling pathways in inducing activation or tolerance, plasticity of NF-kappaB function and the role of chromatin modification and microRNAs in LPS-induced gene reprogramming urges a re-evaluation of endotoxin tolerance. This review integrates these new findings into an up-to-date account of endotoxin tolerance, its molecular basis and clinical implications in different pathologies.
像单核细胞/巨噬细胞这样的先天免疫细胞预先暴露于微量内毒素会导致它们对随后的内毒素刺激产生耐受，这种现象称为“内毒素耐受”。临床上，这种状态与脓毒症患者体内的单核细胞/巨噬细胞有关，它们会导致“免疫抑制”和死亡。内毒素耐受的分子机制仍然不清楚。最近人们认识到炎症是一个自我调节的过程，髓样分化因子88（MyD88）与TIR结构域衔接蛋白诱导干扰素β（TRIF）信号通路在诱导激活或耐受中的相对作用、核因子κB（NF-κB）功能的可塑性以及染色质修饰和微小RNA在脂多糖（LPS）诱导的基因重编程中的作用，促使人们对内毒素耐受进行重新评估。这篇综述将这些新发现整合到关于内毒素耐受、其分子基础以及在不同病理中的临床意义的最新阐述中。
