Interferon-α induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6

被引：793
作者：
Kawai, T
Sato, S
Ishii, KJ
Coban, C
Hemmi, H
Yamamoto, M
Terai, K
Matsuda, M
Inoue, J
Uematsu, S
Takeuchi, O
Akira, S
机构：
[1] Japan Sci & Technol Agcy, Akira Innate Immun Program, ERATO, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan
[3] Osaka Univ, Microbial Dis Res Inst, Dept Tumor Virol, Suita, Osaka 5650871, Japan
[4] Univ Tokyo, Inst Med Sci, Dept Canc Biol, Div Cellular & Mol Biol,Minato Ku, Tokyo 1088639, Japan
来源：
NATURE IMMUNOLOGY | 2004年 / 5卷 / 10期
关键词：
D O I：
10.1038/ni1118
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
引用
收藏
页码：1061 / 1068
页数：8
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