Defective innate immune responses to respiratory syncytial virus infection in ovalbumin-sensitized mice.

BACKGROUND/PURPOSE: Respiratory viral infections have frequently been reported to closely correlate with asthma exacerbations. Distinctive expression of cytokine/chemokine and anomalous responses of innate immunity induced by respiratory viral infections were suggested to play a key role. This study further evaluates the effects of airway sensitization on innate immunity in response to different viruses.

METHODS: Murine sensitization was established using an ovalbumin (OVA) sensitization model. Mice were subsequently infected with either respiratory syncytial virus (RSV) or human metapneumovirus (hMPV). Type I interferon (IFN), cytokines, and chemokines were measured in bronchoalveolar lavage (BAL) fluid. Pulmonary tissue samples were collected for the analysis of viral titers and type I IFN signal transcriptors.

RESULTS: Distinct expressions of cytokine/chemokine responses after viral infection were also found in mice with OVA sensitization. A significant increase of virus replication was found in lungs of RSV-infected sensitized mice. The increment of RSV titer was associated with the decreased levels of type I IFN. Although Toll-like receptor 3 (TLR3) expression was significantly increased in the lungs, the key signal transcriptor, IFN regulatory factor 3, was significantly suppressed in the RSV-infected sensitized mice.

CONCLUSION: A defective antiviral innate response was observed in the murine respiratory allergy model. Suppressed expression of IFN signal transcriptor contributes to decreased production of type I IFN. The defective innate immune response might result in acute viral exacerbations of allergic airway diseases.