A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity
A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity
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DOI：
10.1073/pnas.0810372105
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发表时间：
2008-12-23
影响因子：
11.1
通讯作者：
Honda, Kenya
中科院分区：
文献类型：
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作者：
Negishi, Hideo;Osawa, Tomoko;Honda, Kenya
先天抗病毒免疫的一个难题是核酸敏感toll样受体（TLRs）和rig - 1 /MDA5受体在病毒感染过程中如何合作。传统观点认为，这些受体通路的激活会引发I型IFN （IFN）反应。在这里，我们提供证据证明toll样受体3 （TLR3）依赖性II型IFN信号通路在针对柯萨奇病毒B组血清3型（CVB3）的抗病毒先天性免疫应答中起关键作用，柯萨奇病毒是小核糖核酸病毒科阳性链RNA病毒家族的一员，也是与慢性扩张型心肌病相关的最常见病毒。TLR3缺陷小鼠表现出对CVB3的易感性，并伴有急性心肌炎，而TLR3的转基因表达甚至赋予I型IFN信号缺陷小鼠对CVB3和其他类型病毒的抵抗力，前提是II型IFN信号保持完整。综上所述，我们的研究结果表明rig - 1 / mda5 -I型IFN和tlr3 - II型IFN信号轴在有效的先天抗病毒免疫应答中起着关键的合作作用。
A conundrum of innate antiviral immunity is how nucleic acid-sensing Toll-like receptors (TLRs) and RIG-I/MDA5 receptors cooperate during virus infection. The conventional wisdom has been that the activation of these receptor pathways evokes type I IFN (IFN) responses. Here, we provide evidence for a critical role of a Toll-like receptor 3 (TLR3)-dependent type II IFN signaling pathway in antiviral innate immune response against Coxsackievirus group B serotype 3 (CVB3), a member of the positive-stranded RNA virus family picornaviridae and most prevalent virus associated with chronic dilated cardiomyopathy. TLR3-deficient mice show a vulnerability to CVB3, accompanied by acute myocarditis, whereas transgenic expression of TLR3 endows even type I IFN signal-deficient mice resistance to CVB3 and other types of viruses, provided that type II IFN signaling remains intact. Taken together, our results indicate a critical cooperation of the RIG-I/MDA5-type I IFN and the TLR3-type II IFN signaling axes for efficient innate antiviral immune responses.