The role of Toll-like receptors and MyD88 in innate immune responses
The role of Toll-like receptors and MyD88 in innate immune responses
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DOI：
10.1179/096805100101532315
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Kaisho, T
中科院分区：
文献类型：
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作者：
Akira, S;Hoshino, K;Kaisho, T
Toll样受体（TLR）是识别病原体相关分子模式（PAMPS）的遗传上保守的受体。我们先前产生了缺乏TLR2和TLR4的小鼠，并显示了TLR2和TLR4在微生物识别中的不同作用。TLR4作为脂多糖（LPS）受体的跨膜组分起作用，而TLR2识别来自革兰氏阳性细菌和脂蛋白的肽聚糖。我们还产生了缺乏MyD88的小鼠，MyD88是一种参与IL-1R/TLR信号传导的衔接子。在MyD88缺陷型细胞中，对各种细菌组分的反应完全消除。然而，与其他细菌组分如脂蛋白和细菌DNA介导的信号传导不同，即使在不存在MyD88的情况下，NF-KappaB和MAP激酶的活化也响应于LPS而被诱导，这表明存在MyD88非依赖性途径。我们最近发现MyD88非依赖性通路参与LPS诱导的树突状细胞（DCs）成熟。
Toll-like receptors (TLRs) are phylogenetically conserved receptors that recognize pathogen associated molecular patterns (PAMPS). We previously generated mice lacking TLR2 and TLR4 and showed the differential role of TLR2 and TLR4 in microbial recognition. TLR4 functions as the transmembrane component of the lipopolysaccharide (LPS) receptor, while TLR2 recognizes peptidoglycan from Gram-positive bacteria and lipoprotein. We also generated mice lacking MyD88, an adaptor involved in IL-1R/TLR signalings. The responses to a variety of bacterial components were completely abrogated in MyD88-deficient cells. However, unlike the signaling mediated by other bacterial components such as lipoprotein and bacterial DNA, activation of NF-KappaB and MAP kinases was induced in response to LPS even in the absence of MyD88, which indicates the existence of a MyD88-independent pathway. We have recently found that the MyD88-independent pathway is involved in LPS-induced maturation of dendritic cells (DCs).