Title: Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants.
Authors: Huang, Huaqiong; Saravia, Jordy; You, Dahui; Shaw, Aaron J; Cormier, Stephania A
Published In Immunol Cell Biol, (2015 Feb)
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.
PubMed ID: 25267484
MeSH Terms: Adoptive Transfer; Adult; Animals; Animals, Newborn; Disease Models, Animal; Fetal Blood/cytology; Humans; Infant, Newborn; Inflammasomes/metabolism*; Interferon-gamma/metabolism; Interleukin-17/metabolism*; Mice, Inbred BALB C; Receptors, Antigen, T-Cell, gamma-delta/metabolism*; Respiratory Syncytial Virus Infections/immunology*; Respiratory Syncytial Virus Infections/pathology; Respiratory Syncytial Virus Infections/virology*; Respiratory Syncytial Viruses/immunology*; T-Lymphocytes/immunology