Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases.
Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases.
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DOI：
10.1111/j.1600-065x.2008.00733.x
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发表时间：
2009-01
影响因子：
8.7
通讯作者：
Beutler B
中科院分区：
文献类型：
--
作者：
Beutler B
保护我们免受感染的分子装置也可以通过引起自身免疫性或自身炎症性疾病来伤害我们。现在看来，有时，先天免疫感应臂的缺陷会导致这类疾病。免疫反应的启动通常依赖于微生物，在许多情况下，依赖于toll样受体（TLR）。当TLR信号通路以不受控制的方式刺激宿主细胞时，可能会发生触发免疫激活的正反馈回路。或者，免疫激活可能会持续存在，因为无法根除刺激性感染。或者有时，内源性DNA可能触发特异性免疫反应，在tlr依赖的自身扩增循环中产生进一步的反应。通过随机种系诱变和基因靶向，揭示了引起环相关自身免疫的特定生化缺陷。我们还对反馈循环可能被中断的临界点有了一些见解。
The molecular apparatus that protects us against infection can also injure us by causing autoimmune or autoinflammatory disease. It now seems that at times, defects within the sensing arm of innate immunity contribute to diseases of this type. The initiation of an immune response is often microbe dependent and, in many cases, Toll-like receptor (TLR) dependent. Positive feedback loops triggering immune activation may occur when TLR signaling pathways stimulate host cells in an unchecked manner. Or, immune activation may persist because of failure to eradicate an inciting infection. Or on occasion, endogenous DNA may trigger specific immune responses that beget further responses in a TLR-dependent autoamplification loop. Specific biochemical defects that cause loop-related autoimmunity have been revealed by random germline mutagenesis and by gene targeting. We have also developed some insight into critical points at which feedback loops can be interrupted.