How we detect microbes and respond to them: the Toll-like receptors and their transducers
How we detect microbes and respond to them: the Toll-like receptors and their transducers
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DOI：
10.1189/jlb.0203082
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发表时间：
2003-10-01
影响因子：
5.5
通讯作者：
Ulevitch, RJ
中科院分区：
文献类型：
--
作者：
Beutler, B;Hoebe, K;Ulevitch, RJ
巨噬细胞和树突状细胞处于宿主防御的前线。当它们感觉到宿主入侵时，它们会产生细胞因子，提醒其他先天免疫细胞，并促进适应性免疫反应的发展。尽管脂多糖、肽聚糖、未甲基化的DNA和其他微生物产物早已被认为是天然免疫识别的主要目标，但对于每个分子是如何触发反应的，人们仍然感到困惑。目前已知，Toll样受体(TLRs)是哺乳动物感知感染的主要信号分子。每个TLR识别微生物产生的受限分子子集，在某些情况下，只有一种类型的分子被感知(例如，TLR4只感知内毒素)。TLRs直接激活感染部位附近和远离感染部位的免疫细胞，调动宿主相对庞大的免疫资源，在入侵生物蔓延之前限制和击败它。TLR信号的生化细节已经通过正向和反向遗传方法进行了分析，在宿主和病原体接触后的第一分钟内发生的分子相互作用的完全阐明将很快到来。
Macrophages and dendritic cells are in the front line of host defense. When they sense host invasion, they produce cytokines that alert other innate immune cells and also abet the development of an adaptive immune response. Although lipolysaccharide (LPS), peptidoglycan, unmethylated DNA, and other microbial products were long known to be the primary targets of innate immune recognition, there was puzzlement as to how each molecule triggered a response. It is now known that the Toll-like receptors (TLRs) are the principal signaling molecules through which mammals sense infection. Each TLR recognizes a restricted subset of molecules produced by microbes, and in some circumstances, only a single type of molecule is sensed (e.g., only LPS is sensed by TLR4). TLRs direct the activation of immune cells near to and far from the site of infection, mobilizing the comparatively vast immune resources of the host to confine and defeat an invasive organism before it has become widespread. The biochemical details of TLR signaling have been analyzed through forward and reverse genetic methods, and full elucidation of the molecular interactions that transpire within the first minutes following contact between host and pathogen will soon be at hand.