Respiratory syncytial virus‐induced exaggeration of allergic airway disease is dependent upon CCR1‐associated immune responses

Severe respiratory syncytial virus (RSV) infection has a significant impact on airway function, and may alter subsequent development of asthma. CCR1 mRNA was significantly up‐regulated during primary RSV infection in BALB/c mice, and was also up‐regulated during allergen exposure in sensitized mice. Although CCR1–/– mice exhibited similar levels of airway hyperresponsiveness (AHR) as wild‐type mice in response to cockroach allergen alone, in animals treated with RSV prior to cockroach antigen (CRA) sensitization and challenge, a significant decrease in exacerbated AHR was observed in the CCR1–/– mice. The reduction in AHR after RSV and allergen challenge in CCR1–/– mice was not associated with changes in peribronchial eosinophilia, but was accompanied by significantly decreased IL‐13 levels in the lungs, as well as an absence of mucus cell staining within the airways. When T lymphocyte numbers were compared in animals receiving CRA to animals receiving a combination of RSV and allergen an increase in both CD4 and CD8 T lymphocytes could be detected in wild‐type but not CCR1–/– animals. Thus, these data suggest that CCR1‐mediated responses have a primary role for inducing severe disease during RSV infection, and may be responsible for altering the lung pathophysiological responses to subsequent allergen challenges via IL‐13‐mediated mechanisms.