National Heart and Lung Institute, Imperial College London, St Mary's Hospital, Norfolk Place, London, W2 1PG, UK.
MRC/UCL Lab for Molecular Cell Biology, London, UK.
Mucosal Immunol. 2019 Sep;12(5):1244-1255. doi: 10.1038/s41385-019-0190-0. Epub 2019 Jul 29.
Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections, especially in infants. Lung neutrophilia is a hallmark of RSV disease but the mechanism by which neutrophils are recruited and activated is unclear. Here, we investigate the innate immune signaling pathways underlying neutrophil recruitment and activation in RSV-infected mice. We show that MyD88/TRIF signaling is essential for lung neutrophil recruitment while MAVS signaling, leading to type I IFN production, is necessary for neutrophil activation. Consistent with that notion, administration of type I IFNs to the lungs of RSV-infected Mavs mice partially activates lung neutrophils recruited via the MyD88/TRIF pathway. Conversely, lack of neutrophil recruitment to the lungs of RSV-infected Myd88/Trif mice can be corrected by administration of chemoattractants and those neutrophils become fully activated. Interestingly, Myd88/Trif mice did not have increased lung viral loads during RSV infection, suggesting that neutrophils are dispensable for viral control. Thus, two distinct pathogen sensing pathways collaborate for neutrophil recruitment and full activation during RSV infection.
呼吸道合胞病毒（RSV）是严重下呼吸道感染的主要原因，特别是在婴儿中。肺中性粒细胞增多是 RSV 疾病的标志，但中性粒细胞被募集和激活的机制尚不清楚。在这里，我们研究了 RSV 感染小鼠中性粒细胞募集和激活的固有免疫信号通路。我们表明，MyD88/TRIF 信号通路对于肺中性粒细胞的募集是必需的，而 MAVS 信号通路，导致 I 型 IFN 的产生，对于中性粒细胞的激活是必需的。与这一观点一致的是，向 RSV 感染的 Mavs 小鼠肺部给予 I 型 IFNs 部分激活了通过 MyD88/TRIF 通路募集的肺中性粒细胞。相反，缺乏中性粒细胞募集到 RSV 感染的 Myd88/Trif 小鼠的肺部可以通过趋化因子的给药来纠正，并且这些中性粒细胞被完全激活。有趣的是，在 RSV 感染期间，Myd88/Trif 小鼠的肺部病毒载量没有增加，这表明中性粒细胞对于病毒控制不是必需的。因此，两种不同的病原体感应途径在 RSV 感染期间协同作用以募集和完全激活中性粒细胞。
