Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes.
Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes.
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DOI：
10.1084/jem.20140825
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发表时间：
2015-05-04
期刊：
影响因子：
--
通讯作者：
Johansson C
中科院分区：
文献类型：
--
作者：
Goritzka M;Makris S;Kausar F;Durant LR;Pereira C;Kumagai Y;Culley FJ;Mack M;Akira S;Johansson C
Goritzka等人。描述招募的炎性单核细胞在小鼠的抗病毒免疫和防止RSV感染中的作用。作者证明，这严重依赖于由RIG-I样受体触发的肺泡巨噬细胞产生I型IFN，从而突出了I型干扰素介导的抗病毒活性的一个重要的细胞-外在机制。I型干扰素(IFN)对宿主抵御病毒感染非常重要，它可以限制病毒在受感染细胞中的产生，并促进抗病毒免疫反应。然而，I型干扰素系统也与呼吸道合胞病毒(RSV)引起的严重肺炎性疾病有关。目前尚不清楚哪些细胞在RSV感染时产生I型IFN，以及这如何引导对病毒的免疫反应，并可能导致病理性炎症。在这里，我们证明肺泡巨噬细胞(AM)是小鼠呼吸道合胞病毒感染时I型干扰素的主要来源。AM通过线粒体抗病毒信号蛋白(MAV)偶联的视黄酸诱导基因1(RIG-I)样受体(RLRs)来检测RSV，MAV的缺失极大地损害了RSV的天然免疫限制。这在很大程度上是由于I型干扰素依赖于单核细胞趋化物质的诱导丧失，随后炎性单核细胞(INFMO)向肺部的募集减少。值得注意的是，后者具有强大的抗病毒活性，对于控制感染和减轻疾病严重程度至关重要。因此，InfMo募集构成了I型干扰素介导的抗病毒活性的一个重要的、迄今未被认识的细胞-外在机制。这种宿主抗病毒防御系统的失调可能是RSV诱导的严重肺部炎症发生的基础。
Goritzka et al. describe a role for recruited inflammatory monocytes in antiviral immunity and protection from RSV infection in mice. The authors demonstrate that this is critically dependent on the production of type I IFNs by alveolar macrophages triggered via RIG-I–like receptors, thus highlighting an important cell-extrinsic mechanism of type I IFN–mediated antiviral activity. Type I interferons (IFNs) are important for host defense from viral infections, acting to restrict viral production in infected cells and to promote antiviral immune responses. However, the type I IFN system has also been associated with severe lung inflammatory disease in response to respiratory syncytial virus (RSV). Which cells produce type I IFNs upon RSV infection and how this directs immune responses to the virus, and potentially results in pathological inflammation, is unclear. Here, we show that alveolar macrophages (AMs) are the major source of type I IFNs upon RSV infection in mice. AMs detect RSV via mitochondrial antiviral signaling protein (MAVS)–coupled retinoic acid–inducible gene 1 (RIG-I)–like receptors (RLRs), and loss of MAVS greatly compromises innate immune restriction of RSV. This is largely attributable to loss of type I IFN–dependent induction of monocyte chemoattractants and subsequent reduced recruitment of inflammatory monocytes (infMo) to the lungs. Notably, the latter have potent antiviral activity and are essential to control infection and lessen disease severity. Thus, infMo recruitment constitutes an important and hitherto underappreciated, cell-extrinsic mechanism of type I IFN–mediated antiviral activity. Dysregulation of this system of host antiviral defense may underlie the development of RSV-induced severe lung inflammation.
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影响因子：
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