Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Leukoc Biol. 2011 Oct;90(4):691-701. doi: 10.1189/jlb.0311166. Epub 2011 Aug 15.
IFN-I are pleiotropic cytokines that impact innate and adaptive immune responses. In this article, we discuss TLR7/9 versus TLR3/MDA5 signaling in antiviral responses and diabetes. pDCs are thought to have a critical role in antiviral defense because of their ability to rapidly secrete large amounts of IFN-I through TLR7/9 signaling. A recent study demonstrates that although pDCs are a source of IFN-I in vivo, their overall contribution to viral containment is limited and time-dependent, such that additional cellular sources of IFN-I are required to fully control viral infections. dsRNA sensors, such as TLR3 and MDA5, provide another important trigger for antiviral IFN-I responses, which can be exploited to enhance immune responses to vaccines. In the absence of infection, IFN-I production by pDCs or from signaling through dsRNA sensors has been implicated in the pathogenesis of autoimmune diseases such as diabetes. However, recent data demonstrate that IFN-I production via TLR3 and MDA5 is critical to counter diabetes caused by a virus with preferential tropism for pancreatic β-cells. This highlights the complexity of the host antiviral response and how multiple cellular and molecular components balance protective versus pathological responses.
IFN-I 是一种多功能细胞因子，能够影响先天免疫和适应性免疫反应。本文讨论了 TLR7/9 与 TLR3/MDA5 信号通路在抗病毒反应和糖尿病中的作用。pDCs 因其能够通过 TLR7/9 信号通路迅速分泌大量 IFN-I，而被认为在抗病毒防御中具有关键作用。最近的一项研究表明，尽管 pDCs 是体内 IFN-I 的来源，但它们对病毒控制的总体贡献是有限的且具有时间依赖性，因此需要其他细胞来源的 IFN-I 来完全控制病毒感染。dsRNA 传感器，如 TLR3 和 MDA5，为抗病毒 IFN-I 反应提供了另一个重要触发因素，可用于增强疫苗的免疫反应。在没有感染的情况下，pDCs 通过 TLR3 和 MDA5 信号通路产生 IFN-I 已被认为与自身免疫性疾病（如糖尿病）的发病机制有关。然而，最近的数据表明，通过 TLR3 和 MDA5 产生 IFN-I 对于对抗病毒优先靶向胰岛β细胞的病毒引起的糖尿病至关重要。这突显了宿主抗病毒反应的复杂性，以及多种细胞和分子成分如何平衡保护性和病理性反应。
