Cutting edge: A toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling
Cutting edge: A toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling
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DOI：
10.4049/jimmunol.170.7.3451
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发表时间：
2003-04-01
影响因子：
4.4
通讯作者：
Aderem, A
中科院分区：
文献类型：
--
作者：
Bochud, PY;Hawn, TR;Aderem, A
toll样受体（TLRs）是先天免疫应答微生物病原体的关键介质。我们研究了TLRs在识别麻风分枝杆菌中的作用，以及TLR2Arg(677)Trp的意义，TLR2Arg(677)Trp是最近发现的一种与麻风性麻风相关的人类多态性。在小鼠中，tlr2缺陷巨噬细胞对麻风分枝杆菌的反应中tnf - α的产生基本上不存在。同样，在转染的中国仓鼠卵巢和人胚胎肾293细胞中，人TLR2介导的麻风分枝杆菌依赖的NF-kappaB激活在CD14存在下增强。相反，人TLR2- arg (677)Trp对NF-kappaB的激活在麻风分枝杆菌和结核分枝杆菌的反应中被消除。这种TLR2变异的功能受损为与麻风病相关的细胞免疫反应不良提供了分子机制，并可能对理解其他分枝杆菌感染的发病机制具有重要意义。
Toll-like receptors (TLRs) are key mediators of the innate immune response to microbial pathogens. We investigated the role of TLRs in the recognition of Mycobacterium leprae and the significance of TLR2Arg(677)Trp, a recently discovered human polymorphism that is associated with lepromatous leprosy. In mice, TNF-alpha production in response to M. leprae was essentially absent in TLR2-deficient macrophages. Similarly, human TLR2 mediated M. leprae-dependent activation of NF-kappaB in transfected Chinese hamster ovary and human embryonic kidney 293 cells, with enhancement of this signaling in the presence of CD14 In contrast, activation of NF-kappaB by human TLR2-Arg(677)Trp was abolished in response to M. leprae and Mycobacterium tuberculosis. The impaired function of this TLR2 variant provides a molecular mechanism for the poor cellular immune response associated with lepromatous leprosy and may have important implications for understanding the pathogenesis of other mycobacterial infections.