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

Mucosal Immunol. 2019 Sep;12(5):1244-1255. doi: 10.1038/s41385-019-0190-0. Epub 2019 Jul 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Animals
  • Biomarkers
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Immunophenotyping
  • Inflammation Mediators / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / metabolism*
  • Neutrophil Infiltration / immunology*
  • Neutrophils / immunology*
  • Neutrophils / metabolism*
  • Neutrophils / pathology
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism*
  • Respiratory Syncytial Viruses / immunology
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Biomarkers
  • Cytokines
  • IPS-1 protein, mouse
  • Inflammation Mediators
  • Myeloid Differentiation Factor 88
  • TICAM-1 protein, mouse