Beutler B, Hoebe K, Du X, Ulevitch R J
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Leukoc Biol. 2003 Oct;74(4):479-85. doi: 10.1189/jlb.0203082. Epub 2003 Jul 1.
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.
巨噬细胞和树突状细胞处于宿主防御的第一线。当它们感知到宿主受到入侵时，会产生细胞因子，这些细胞因子会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（LPS）、肽聚糖、未甲基化的DNA和其他微生物产物长期以来被认为是先天免疫识别的主要靶点，但对于每个分子如何触发反应仍存在困惑。现在已知Toll样受体（TLR）是哺乳动物感知感染的主要信号分子。每个TLR识别微生物产生的有限分子子集，在某些情况下，只感知单一类型的分子（例如，TLR4只感知LPS）。TLR指导感染部位附近和远处免疫细胞的激活，调动宿主相对庞大的免疫资源，在入侵生物体扩散之前将其限制并击败。通过正向和反向遗传方法对TLR信号传导的生化细节进行了分析，宿主与病原体接触后的最初几分钟内发生的分子相互作用的全面阐明即将实现。
