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.
Bibliographical noteFunding Information:
We thank S. Akira and Y. Kumagai (World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan) for providing Mavs−/− and Myd88/Trif−/− mice. We thank Caetano Reis e Sousa, Robert Snelgrove and Ryan Thwaites for critically reading the manuscript. We also thank the other members of the Respiratory Infections section for suggestions and critique. Finally, we thank Yanping Guo of the St Mary’s flow cytometry facility for her help and the staff of the St Mary’s animal facility for their assistance. F.C.M.K. was supported by a PhD Fellowship from the Wellcome Trust (109058/Z/15/Z), F.K. and S.M. were supported by PhD Fellowships from the National Heart and Lung Institute Foundation (registered charity number 1048073), and C.J. was supported by a grant from the Rosetrees Trust (M370).
© 2019, The Author(s).