Title: Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33.
Authors: Saravia, Jordy; You, Dahui; Shrestha, Bishwas; Jaligama, Sridhar; Siefker, David; Lee, Greg I; Harding, Jeffrey N; Jones, Tamekia L; Rovnaghi, Cynthia; Bagga, Bindiya; DeVincenzo, John P; Cormier, Stephania A
Published In PLoS Pathog, (2015 Oct)
Abstract: Respiratory syncytial virus (RSV) is the most common cause of infant hospitalizations and severe RSV infections are a significant risk factor for childhood asthma. The pathogenic mechanisms responsible for RSV induced immunopathophysiology remain elusive. Using an age-appropriate mouse model of RSV, we show that IL-33 plays a critical role in the immunopathogenesis of severe RSV, which is associated with higher group 2 innate lymphoid cells (ILC2s) specifically in neonates. Infection with RSV induced rapid IL-33 expression and an increase in ILC2 numbers in the lungs of neonatal mice; this was not observed in adult mice. Blocking IL-33 with antibodies or using an IL-33 receptor knockout mouse during infection was sufficient to inhibit RSV immunopathogenesis (i.e., airway hyperresponsiveness, Th2 inflammation, eosinophilia, and mucus hyperproduction); whereas administration of IL-33 to adult mice during RSV infection was sufficient to induce RSV disease. Additionally, elevated IL-33 and IL-13 were observed in nasal aspirates from infants hospitalized with RSV; these cytokines declined during convalescence. In summary, IL-33 is necessary, either directly or indirectly, to induce ILC2s and the Th2 biased immunopathophysiology observed following neonatal RSV infection. This study provides a mechanism involving IL-33 and ILC2s in RSV mediated human asthma.
PubMed ID: 26473724
MeSH Terms: Aging; Animals; Animals, Newborn; Disease Models, Animal; Female; Flow Cytometry; Humans; Infant; Interleukin-33/immunology*; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Respiratory Function Tests; Respiratory Syncytial Virus Infections/immunology*; Respiratory Syncytial Viruses/immunology; Th2 Cells/immunology