Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6.
Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6.
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DOI：
10.1084/jem.192.4.595
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发表时间：
2000-08-21
期刊：
影响因子：
--
通讯作者：
Wagner H
中科院分区：
文献类型：
--
作者：
Häcker H;Vabulas RM;Takeuchi O;Hoshino K;Akira S;Wagner H
未成熟的抗原呈递细胞（APC）向专职APC的转变对于启动针对病原体的细胞介导的免疫应答是必不可少的。通过Toll样受体（TLR）/白细胞介素1受体（IL-1 R）途径的分子的信号转导对于通过病原体衍生的模式配体如脂多糖（LPS）或通过T辅助细胞的CD 40连接来激活APC是关键的。细菌DNA（CpG-DNA）诱导APC分化为专业APC的能力是一个有趣的发现。然而，所涉及的信号通路知之甚少。我们发现CpG-DNA通过髓样分化标志物88（MyD 88）和肿瘤坏死因子受体相关因子6（TRAF 6）激活TLR/IL-1 R信号通路，导致IκB激酶复合物和c-jun NH 2-末端激酶的激活。此外，TLR 2和TLR 4缺陷型小鼠的细胞被CpG-DNA激活，而MyD 88缺陷型小鼠的细胞不响应。这些数据表明，CpG-DNA通过TLR/IL-1 R途径在APC中以类似于LPS和T辅助细胞介导的CD 40连接的方式启动信号传导。外源细菌DNA激活TLR/IL-1 R信号通路可能是启动体内对抗感染性病原体的先天防御机制的一种方式。
Transition of immature antigen presenting cells (APCs) to the state of professional APCs is essential for initiation of cell-mediated immune responses to pathogens. Signal transduction via molecules of the Toll-like receptor (TLR)/interleukin 1 receptor (IL-1R) pathway is critical for activation of APCs either by pathogen-derived pattern ligands like lipopolysaccharides (LPS) or by CD40 ligation through T helper cells. The capacity of bacterial DNA (CpG-DNA) to induce APCs to differentiate into professional APCs represents an interesting discovery. However, the signaling pathways involved are poorly understood. Here we show that CpG-DNA activates the TLR/IL-1R signaling pathway via the molecules myeloid differentiation marker 88 (MyD88) and tumor necrosis factor receptor–associated factor 6 (TRAF6), leading to activation of kinases of the IκB kinase complex and the c-jun NH2-terminal kinases. Moreover, cells of TLR2- and TLR4-deficient mice are activated by CpG-DNA, whereas cells of MyD88-deficient mice do not respond. The data suggest that CpG-DNA initiates signaling via the TLR/IL-1R pathway in APCs in a manner similar to LPS and to T helper cell–mediated CD40 ligation. Activation of the TLR/IL-1R signaling pathway by foreign bacterial DNA may be one way to initiate innate defense mechanisms against infectious pathogens in vivo.
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