Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33: e1005217

• Published in: PLoS pathogens 2015-10, Vol.11 (10)
• Main 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
• Format: Article
• Language: English
• Subjects: Age; Asthma; Children & youth; Cytokines; Experiments; Infants; Infections; Laboratory animals; Lungs; Neonates; Respiratory syncytial virus; Risk factors; Rodents; Studies; Viral infections
• ISSN: 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1005217

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.