Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages
Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages
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DOI：
10.1073/pnas.96.25.14459
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发表时间：
1999-12-07
影响因子：
11.1
通讯作者：
Aderem, A
中科院分区：
文献类型：
--
作者：
Underhill, DM;Ozinsky, A;Aderem, A
对分枝杆菌细胞壁成分的识别导致巨噬细胞分泌肿瘤坏死因子α(TNF-α)和其他细胞因子，这些是保护性炎症反应发展所必需的。我们发现Toll样受体是结核分枝杆菌诱导巨噬细胞产生肿瘤坏死因子-α所必需的。在小鼠巨噬细胞系中表达显性阴性形式的MyD88(Toll样受体信号所需的9个信号成分)可阻断结核分枝杆菌诱导的肿瘤坏死因子-α的产生。我们确定Toll样受体-2(TLR2)是这种诱导所需的特异性Toll样受体，因为抑制TLR2(TLR2-P681H)的表达可以阻断整个结核分枝杆菌诱导的肿瘤坏死因子-α的产生。再远一点。我们发现，依赖于TLR2的信号介导了对富含脂阿糖甘露聚糖的分枝杆菌细胞壁部分的反应。分枝杆菌半乳聚糖-肽多聚糖复合体。或结核分枝杆菌的总脂。因此，尽管许多分枝杆菌细胞壁组分被鉴定为炎症性的，但都需要TLR2来诱导巨噬细胞中的肿瘤坏死因子-α。这些数据表明，TLR2对于诱导对分枝杆菌的保护性免疫反应是必不可少的。
The recognition of mycobacterial cell wall components causes macrophages to secrete tumor necrosis factor alpha (TNF-alpha) and other cytokines that are essential for the development of a protective inflammatory response. We show that toll-like receptors are required for the induction of TNF-alpha in macrophages by Mycobacterium tuberculosis. Expression of a dominant negative form of MyD88 (9 signaling component required for toll-like receptor signaling) in a mouse macrophage cell line blocks TNF-alpha production induced by M. tuberculosis. We identify toll-like receptor-2 (TLR2) as the specific toll-like receptor required for this induction by showing that expression of an inhibitory TLR2 (TLR2-P681H) blocks TNF-alpha production induced by whole M. tuberculosis. Further. we show that TLR2-dependent signaling mediates responses to mycobacterial cell wall fractions enriched for lipoarrabinomannan. mycolylarabinogalactan-peptidoglycan complex. or M. tuberculosis total lipids. Thus, although many mycobacterial cell wall fractions are identified to be inflammatory, all require TLR2 for induction of TNF-alpha in macrophages. These data suggest that TLR2 is essential for the induction of a protective immune response to mycobacteria.