Neutrophil recruitment and activation are differentially dependent on MyD88/TRIF and MAVS signaling during RSV infection.,Mucosal Immunology

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Neutrophil recruitment and activation are differentially dependent on MyD88/TRIF and MAVS signaling during RSV infection.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-07-29 , DOI: 10.1038/s41385-019-0190-0
Freja C M Kirsebom ₁ , Fahima Kausar ₁ , Rinat Nuriev ₁ , Spyridon Makris _{1,

2} , Cecilia Johansson ₁

Affiliation

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.

中文翻译：

在 RSV 感染期间，中性粒细胞募集和激活有差异地依赖于 MyD88/TRIF 和 MAVS 信号。

呼吸道合胞病毒 (RSV) 是严重下呼吸道感染的主要原因，尤其是在婴儿中。肺中性粒细胞增多是 RSV 疾病的一个标志，但中性粒细胞募集和激活的机制尚不清楚。在这里，我们研究了 RSV 感染小鼠中中性粒细胞募集和激活的先天免疫信号通路。我们表明 MyD88/TRIF 信号对于肺中性粒细胞募集至关重要，而导致 I 型 IFN 产生的 MAVS 信号对于中性粒细胞激活是必需的。与该观点一致，对 RSV 感染的 Mavs-/- 小鼠的肺部施用 I 型干扰素可部分激活通过 MyD88/TRIF 途径募集的肺中性粒细胞。反过来，RSV 感染的 Myd88/Trif-/- 小鼠肺部缺乏嗜中性粒细胞募集，可通过施用趋化剂来纠正，并且这些嗜中性粒细胞变得完全激活。有趣的是，Myd88/Trif-/- 小鼠在 RSV 感染期间肺部病毒载量没有增加，这表明中性粒细胞对于病毒控制是可有可无的。因此，两种不同的病原体感应途径在 RSV 感染期间协作用于中性粒细胞募集和完全激活。

更新日期：2019-11-18

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