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

Kirseborn, FCM; Kausar, F; Nuriev, R; Makris, S; Johansson, C; (2019) Neutrophil recruitment and activation are differentially dependent on MyD88/TRIF and MAVS signaling during RSV infection. Mucosal Immunology , 12 pp. 1244-1255. 10.1038/s41385-019-0190-0. Green open access

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Abstract

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.

Type: Article
Title: Neutrophil recruitment and activation are differentially dependent on MyD88/TRIF and MAVS signaling during RSV infection
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41385-019-0190-0
Publisher version: https://doi.org/10.4000/tc.495610.1038/s41385-019-...
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10082849
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