Interferon-α induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6
Interferon-α induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6
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DOI：
10.1038/ni1118
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发表时间：
2004-10-01
影响因子：
30.5
通讯作者：
Akira, S
中科院分区：
文献类型：
--
作者：
Kawai, T;Sato, S;Akira, S
Toll样受体（TLR）参与了微生物病原体的识别。 TLRS，TLR7，TLR8和TLR9的子集通过产生干扰素-Alpha（IFN-Alpha）引起抗病毒反应。 IFN-Alpha的产生取决于含Toll-Interleukin-1受体结构域MyD88的Toll-Interleukin-1受体。在这里，我们表明MYD88与转录因子IRF7形成了一个复合物，但没有IRF3。 MyD88的死亡结构域与IRF7的抑制域相互作用，这种相互作用导致IFN-Alpha依赖性启动子的激活。此外，适配器分子TRAF6还结合并激活的IRF7。 IRF7激活需要TRAF6的泛素连接酶活性。这些结果表明，TLR介导的IFN-α诱导需要形成由MyD88，TRAF6和IRF7以及TRAF6依赖性的泛素化组成的复合物。
Toll-like receptors (TLRs) are involved in the recognition of microbial pathogens. A subset of TLRs, TLR7, TLR8 and TLR9, induces antiviral responses by producing interferon-alpha (IFN-alpha). Production of IFN-alpha is dependent on the Toll-interleukin-1 receptor domain-containing adaptor MyD88. Here we show that MyD88 formed a complex with the transcription factor IRF7 but not with IRF3. The death domain of MyD88 interacted with an inhibitory domain of IRF7, and this interaction resulted in activation of the IFN-alpha-dependent promoters. Furthermore, the adaptor molecule TRAF6 also bound and activated IRF7. Ubiquitin ligase activity of TRAF6 was required for IRF7 activation. These results indicate that TLR-mediated IFN-alpha induction requires the formation of a complex consisting of MyD88, TRAF6 and IRF7 as well as TRAF6-dependent ubiquitination.