title: Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants.
abstract: Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. Interleukin (IL)-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interest in its role in RSV infection. Using a neonatal mouse model of RSV, we demonstrate that neonates fail to develop IL-17A responses compared with adult mice; the main immediate IL-17A contributor in adults were γδ T cells. Antibody neutralization of IL-17A in adult mice caused increased lung inflammation and airway mucus from RSV, whereas exogenous IL-17A administration to RSV-infected neonates caused decreased inflammation but no change in airway mucus. We also observed a lack of pro-inflammatory cytokine production (IL-1β, IL-6) from infected neonates. Using human cord blood mononuclear cells (CBMCs) and adult peripheral blood mononuclear cells (PBMCs), we compared inflammasome activation by direct retinoic acid-inducible gene I agonism; CBMCs failed to induce pro-inflammatory cytokines or IL-17A(+) γδ T cells compared with PBMCs. Our results indicate that RSV disease severity is in part mediated by a lack of inflammasome activation and IL-17A production in neonates.
authors.affiliation: 1] Department of Respiratory Disease, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China [2] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA [3] Children's Research Foundation Institute, Le Bonheur Children's Hospital, Memphis, TN, USA.
authors.forename: Huaqiong
authors.initials: H
authors.lastname: Huang
authors.affiliation: 1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA [2] Children's Research Foundation Institute, Le Bonheur Children's Hospital, Memphis, TN, USA.
authors.forename: Jordy
authors.initials: J
authors.lastname: Saravia
authors.affiliation: 1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA [2] Children's Research Foundation Institute, Le Bonheur Children's Hospital, Memphis, TN, USA.
authors.forename: Dahui
authors.initials: D
authors.lastname: You
authors.affiliation: 1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA [2] Children's Research Foundation Institute, Le Bonheur Children's Hospital, Memphis, TN, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Shaw
authors.affiliation: 1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA [2] Children's Research Foundation Institute, Le Bonheur Children's Hospital, Memphis, TN, USA.
authors.forename: Stephania A
authors.initials: SA
authors.lastname: Cormier
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D058847:Inflammasomes / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D058847:Inflammasomes; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma