Identification of a TLR-independent pathway for Borrelia burgdorferi-induced expression of matrix metalloproteinases and inflammatory mediators through binding to integrin α3β1
Identification of a TLR-independent pathway for Borrelia burgdorferi-induced expression of matrix metalloproteinases and inflammatory mediators through binding to integrin α3β1
复制标题
DOI：
10.4049/jimmunol.177.1.657
复制
发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Hu, Linden T.
中科院分区：
文献类型：
--
作者：
Behera, Aruna K.;Hildebrand, Ethan;Hu, Linden T.
伯氏疏螺旋体在局部刺激强烈的炎症反应。疏螺旋体脂蛋白与TLR-2的结合是宿主对B应答中的一个重要途径。burgdorferi。然而，虽然TLR-2在控制感染方面显然很重要，但在缺乏TLR-2或共享TLR衔接分子MyD 88的情况下，炎症实际上会恶化，这表明存在调节炎症的替代途径。整合素是细胞表面受体，其在细胞与细胞通信中起重要作用，并且可以激活炎症信号传导途径。在这项研究中，我们首次报道了B。burgdorferi与整联蛋白α（3）β（1）结合，并与B结合。Burgdorferi与该整联蛋白的结合导致在原代人软骨细胞中诱导促炎细胞因子、趋化因子和末端效应分子如基质金属蛋白酶。这些相同的分子的表达不受MyD 88在小鼠关节软骨的情况下，这表明这两个途径独立地激活宿主炎症反应，伯氏螺旋体。B。α，信号传导由JNK介导，而不是p38 MAPK。总之，我们已经鉴定了B的新宿主受体。burgdorferi，整合素a，p，; B的结合。Burgdorferi与整联蛋白α 3g的结合导致炎性介质的释放，并被认为是生物体激活先天免疫应答的TLR-非依赖性途径。
Borrelia burgdorferi stimulates a robust inflammatory response at sites of localization. Binding of borrelial lipoproteins to TLR-2 is one pathway important in the host response to B. burgdorferi. However, while TLR-2 is clearly important in control of infection, inflammation is actually worsened in the absence of TLR-2 or the shared TLR adapter molecule, MyD88, suggesting that there are alternative pathways regulating inflammation. Integrins are cell surface receptors that play an important role in cell to cell communications and that can activate inflammatory signaling pathways. In this study, we report for the first time that B. burgdorferi binds to integrin alpha(3)beta(1) and that binding of B. burgdorferi to this integrin results in induction of proinflammatory cytokines, chemokines, and end-effector molecules such as matrix metalloproteinases in primary human chondrocyte cells. Expression of these same molecules is not affected by the absence of MyD88 in murine articular cartilage, suggesting that the two pathways act independently in activating host inflammatory responses, to A burgdorferi. B. burgdorferi-induced'a, signaling is mediated by JNK, but not p38 MAPK. In summary, we have identified a new host receptor for B. burgdorferi, integrin a,p,; binding of B. burgdorferi to integrin a3g, results in the release of inflammatory mediators and is proposed as a TLR-independent pathway for activation of the innate immune response by the organism.