IL-17E (IL-25) and IL-17RB promote respiratory syncytial virus-induced pulmonary disease

One of the most severe pathologic responses of RSV infection is associated with overproduction of cytokines and inflammation, leading to mucus hypersecretion. This study investigated the role of IL-25 in the development of RSV-associated immunopathology. IL-25 and its receptor IL-17RB were increased following RSV infection, and IL-25 blockade using neutralizing antibodies reduced RSV-associated pathology, AHR, and type 2 cytokine production. Likewise, IL-17RB(-/-) mice demonstrated a modified inflammatory response during RSV infection characterized by decreased Th2 and increased Th17 cytokine production. Additionally, the IL-17RB(-/-) mice demonstrated significantly reduced inflammation and cytokine production in a model of RSV-driven asthma exacerbation. These results indicate that IL-25 regulates the inflammatory response to RSV infection and that its inhibition may enable a reduction in the severity of RSV-associated pulmonary inflammation, including during viral-induced asthma exacerbation. RSV infection induces IL-25 that contributes to the pathogenesis of pulmonary disease during primary infection and asthma-like exacerbations.