Local IL-17A potentiates early neutrophil recruitment to the respiratory tract during severe RSV infection

PLoS One. 2013 Oct 23;8(10):e78461. doi: 10.1371/journal.pone.0078461. eCollection 2013.

Abstract

Respiratory syncytial virus (RSV) bronchiolitis triggers a strong innate immune response characterized by excessive neutrophil infiltration which contributes to RSV induced pathology. The cytokine IL-17A enhances neutrophil infiltration into virus infected lungs. IL-17A is however best known as an effector of adaptive immune responses. The role of IL-17A in early immune modulation in RSV infection is unknown. We aimed to elucidate whether local IL-17A facilitates the innate neutrophil infiltration into RSV infected lungs prior to adaptive immunity. To this end, we studied IL-17A production in newborns that were hospitalized for severe RSV bronchiolitis. In tracheal aspirates we measured IL-17A concentration and neutrophil counts. We utilized cultured human epithelial cells to test if IL-17A regulates RSV infection-induced IL-8 release as mediator of neutrophil recruitment. In mice we investigated the cell types that are responsible for early innate IL-17A production during RSV infection. Using IL-17A neutralizing antibodies we tested if IL-17A is responsible for innate neutrophil infiltration in mice. Our data show that increased IL-17A production in newborn RSV patient lungs correlates with subsequent neutrophil counts recruited to the lungs. IL-17A potentiates RSV-induced production of the neutrophil-attracting chemokine IL-8 by airway epithelial cells in vitro. Various lung-resident lymphocytes produced IL-17A during early RSV infection in Balb/c mice, of which a local population of CD4 T cells stood out as the predominant RSV-induced cell type. By removing IL-17A during early RSV infection in mice we showed that IL-17A is responsible for enhanced innate neutrophil infiltration in vivo. Using patient material, in vitro studies, and an animal model of RSV infection, we thus show that early local IL-17A production in the airways during RSV bronchiolitis facilitates neutrophil recruitment with pathologic consequences to infant lungs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Flow Cytometry
  • Humans
  • Immunity, Innate / immunology*
  • Infant, Newborn
  • Interleukin-17 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Neutrophil Infiltration / immunology*
  • Real-Time Polymerase Chain Reaction
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory System / immunology*

Substances

  • Antibodies, Neutralizing
  • Interleukin-17

Grant support

This study was funded by the WKZ research fund (grant number R1812). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.