Respiratory syncytial virus infection modifies and accelerates pulmonary disease via DC activation and migration.

In the present studies, we have established that RSV can elicit a more pathogenic environment dependent on improper DC-associated sensitization. Our initial studies demonstrated that RSV, but not influenza, infection during an allergen exposure into the airway induced a more severe allergen response. The RSV-induced exacerbation included an increased Th2 cytokine response and pathophysiology as monitored by AHR and mucus overproduction. DCs played a central role in the allergen-induced responses, as instilling RSV-infected BMDC into the airway could recapitulate a live virus challenge. With the use of CCR6-/- mice that have a primary defect in the recruitment of mDC subsets, reduced exacerbation of disease was observed when RSV was administered along with allergen. Furthermore, sensitization of mice with RSV-infected BMDC into the airway produced a more severe immune response to a live virus challenge. Subsequently, using RSV-infected BMDC from CCR7-/- mice (that do not migrate efficiently to LNs) to sensitize the exacerbated response demonstrated that the response was dependent on DC migration to the LN. Finally, the ability of RSV-infected DCs to elicit an exacerbated, allergen-induced pathogenic response could be maintained for as long as 3 weeks, suggesting that RSV-infected DCs themselves created an altered immune environment that impacts off-target mucosal responses that could have prolonged effects.