Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
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DOI：
10.1038/35099560
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发表时间：
2001-10-18
期刊：
影响因子：
64.8
通讯作者：
Flavell, RA
中科院分区：
文献类型：
--
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
Toll样受体是一类天然免疫识别受体，识别与微生物病原体相关的分子模式，并诱导抗微生物免疫反应(1，2)。双链RNA(DsRNA)是一种与病毒感染有关的分子模式，因为大多数病毒在其复制过程中的某个时候会产生dsRNA(3)。在这里，我们表明哺乳动物TLR3识别dsRNA，受体的激活诱导核因子-kappaB的激活和I型干扰素(IFN)的产生。TLR3基因缺陷(TLR3(-/-))小鼠对多聚肌苷多胞苷(Poly(I：C))的反应降低，对D-氨基半乳糖(D-GalN)致敏的PolyI：C的致死作用耐受，炎性细胞因子的产生减少。MyD88是一种连接蛋白，被所有已知的TLRs所共享(1)。当被PolyI：C激活时，TLR3通过依赖于MyD88的信号通路诱导细胞因子的产生。此外，Poly(I：C)可以独立于MyD88诱导核因子-kappaB和丝裂原活化蛋白(MAP)激酶的激活，并促使树突状细胞成熟。
Toll-like receptors (TLRs) are a family of innate immune-recognition receptors that recognize molecular patterns associated with microbial pathogens, and induce antimicrobial immune responses(1,2). Double-stranded RNA (dsRNA) is a molecular pattern associated with viral infection, because it is produced by most viruses at some point during their replication(3). Here we show that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-kappaB and the production of type I interferons (IFNs). TLR3-deficient (TLR3(-/-)) mice showed reduced responses to polyinosine-polycytidylic acid (poly(I:C)), resistance to the lethal effect of poly(I:C) when sensitized with D-galactosamine (D-GalN), and reduced production of inflammatory cytokines. MyD88 is an adaptor protein that is shared by all the known TLRs(1). When activated by poly(I:C), TLR3 induces cytokine production through a signalling pathway dependent on MyD88. Moreover, poly(I:C) can induce activation of NF-kappaB and mitogen-activated protein (MAP) kinases independently of MyD88, and cause dendritic cells to mature.