title: Local IL-17A potentiates early neutrophil recruitment to the respiratory tract during severe RSV infection.
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.
authors.affiliation: Department of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, the Netherlands.
authors.forename: Arie Jan
authors.initials: AJ
authors.lastname: Stoppelenburg
authors.forename: Vahid
authors.initials: V
authors.lastname: Salimi
authors.forename: Marije
authors.initials: M
authors.lastname: Hennus
authors.forename: Maud
authors.initials: M
authors.lastname: Plantinga
authors.forename: Ron
authors.initials: R
authors.lastname: Huis in 't Veld
authors.forename: Jona
authors.initials: J
authors.lastname: Walk
authors.forename: Jenny
authors.initials: J
authors.lastname: Meerding
authors.forename: Frank
authors.initials: F
authors.lastname: Coenjaerts
authors.forename: Louis
authors.initials: L
authors.lastname: Bont
authors.forename: Marianne
authors.initials: M
authors.lastname: Boes
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007231:Infant, Newborn; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D020381:Interleukin-17