Mint3 potentiates TLR3/4-and RIG-I-induced IFN-β expression and antiviral immune responses
Mint3 potentiates TLR3/4-and RIG-I-induced IFN-β expression and antiviral immune responses
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Mint3 增强 TLR3/4 和 RIG-I 诱导的 IFN-β 表达和抗病毒免疫反应。
DOI：
10.1073/pnas.1601556113
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发表时间：
2016-10-18
影响因子：
11.1
通讯作者：
Zhao, Wei
中科院分区：
文献类型：
--
作者：
Huai, Wanwan;Song, Hui;Zhao, Wei
I 型干扰素 (IFN-α/β) 在消除入侵病毒方面发挥着至关重要的作用。包括巨噬细胞在内的多种免疫细胞通过多种模式识别受体（例如Toll样受体（TLR）和视黄酸诱导基因-I（RIG-I）样受体）识别病毒感染，并启动I型IFN分泌和随后的抗病毒免疫反应。然而，宿主免疫细胞产生足够量的I型干扰素然后有效消除病毒的机制仍有待进一步阐明。在本研究中，我们发现在病毒感染巨噬细胞期间，munc18-1 相互作用蛋白 3 (Mint3) 的表达可以被显着诱导。 Mint3 通过促进 TNF 受体相关因子 3 (TRAF3) 的 K63 连接多聚泛素化来增强 TLR3/4 和 RIG-I 诱导的 IRF3 激活和 IFN-β 产生。一致的是，Mint3 缺陷大大减弱了抗病毒免疫反应并增加了病毒复制。因此，我们已经确定 Mint3 是 TLR3/4 和 RIG-I 诱导的 IFN-β 产生的生理正调节因子，并概述了控制抗病毒免疫反应的反馈机制。
Type I IFNs (IFN-alpha/beta) play crucial roles in the elimination of invading viruses. Multiple immune cells including macrophages recognize viral infection through a variety of pattern recognition receptors, such as Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors, and initiate type I IFN secretion and subsequent antiviral immune responses. However, the mechanisms by which host immune cells can produce adequate amounts of type I IFNs and then eliminate viruses effectively remain to be further elucidated. In the present study, we show that munc18-1-interacting protein 3 (Mint3) expression can be markedly induced during viral infection in macrophages. Mint3 enhances TLR3/4- and RIG-I-induced IRF3 activation and IFN-beta production by promoting K63-linked polyubiquitination of TNF receptor-associated factor 3 (TRAF3). Consistently, Mint3 deficiency greatly attenuated antiviral immune responses and increased viral replication. Therefore, we have identified Mint3 as a physiological positive regulator of TLR3/4 and RIG-I-induced IFN-beta production and have outlined a feedback mechanism for the control of antiviral immune responses.