Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products
Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products
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DOI：
10.1074/jbc.274.47.33419
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发表时间：
1999-11-19
影响因子：
4.8
通讯作者：
Golenbock, DT
中科院分区：
文献类型：
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作者：
Lien, E;Sellati, TJ;Golenbock, DT
toll样受体（TLRs） 2和4是脂多糖的信号转导器，脂多糖是革兰氏阴性菌外膜的主要促炎成分。我们观察到来自伯氏疏螺旋体、梅毒螺旋体和发酵支原体的膜脂蛋白/脂肽激活了异种表达TLR2的细胞，而不是表达TLR1或TLR4的细胞。这些表达TLR2的细胞也受到活的运动伯氏疏螺旋体的刺激，表明TLR2对脂蛋白的识别与天然伯氏疏螺旋体感染有关。重要的是，TLR2抗体抑制细菌脂蛋白/脂肽诱导的肿瘤坏死因子从人外周血单个核细胞释放，TLR2缺失的中国仓鼠巨噬细胞对脂蛋白/脂肽的攻击不敏感。此外，在整个鸟分枝杆菌和金黄色葡萄球菌中发现了tlr2依赖性反应，这表明该受体可以作为广泛的细菌产物的信号换能器。我们得出结论，多种病原体通过TLR2激活细胞，并提出该分子是宿主对微生物入侵免疫反应的中心模式识别受体。
Toll-like receptors (TLRs) 2 and 4 are signal transducers for lipopolysaccharide, the major proinflammatory constituent in the outer membrane of Gram-negative bacteria. We observed that membrane lipoproteins/lipopeptides from Borrelia burgdorferi, Treponema pallidum, and Mycoplasma fermentans activated cells heterologously expressing TLR2 but not those expressing TLR1 or TLR4. These TLR2-expressing cells were also stimulated by living motile B. burgdorferi, suggesting that TLR2 recognition of lipoproteins is relevant to natural Borrelia infection, Importantly, a TLR2 antibody inhibited bacterial lipoprotein/lipopeptide-induced tumor necrosis factor release from human peripheral blood mononuclear cells, and TLR2-null Chinese hamster macrophages were insensitive to lipoprotein/lipopeptide challenge. The data suggest a role for the native protein in cellular activation by these ligands, In addition, TLR2-dependent responses were seen using whole Mycobacterium avium and Staphylococcus aureus, demonstrating that this receptor can function as a signal transducer for a wide spectrum of bacterial products. We conclude that diverse pathogens activate cells through TLR2 and propose that this molecule is a central pattern recognition receptor in host immune responses to microbial invasion.