Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus

Abstract
Respiratory syncytial virus (RSV) infection is widely spread and is a major cause of bronchiolitis in infants and high-risk adults, often leading to hospitalization. RSV infection leads to obstruction and inflammation of the airways and induction of innate and acquired immune responses. Because dendritic cells (DCs) are essential in the elicitation of these immune responses, we investigated the presence and the role of dendritic cell subtypes upon RSV infection in the lung. Here, we report that RSV infection increased the number of both conventional and plasmacytoid dendritic cells in the lung and the lung-draining lymph nodes. In particular, the increase in plasmacytoid dendritic cell numbers was sustained and lasted until 30 d after infection. Depletion of plasmacytoid dendritic cells resulted in decreased RSV clearance. In addition, depletion of plasmacytoid dendritic cells resulted in an exacerbation of all manifestations of immune-mediated pathology caused by RSV infection. In conclusion, this study demonstrates that both conventional and plasmacytoid dendritic cells are attracted to the site of RSV infection. It is demonstrated that plasmacytoid dendritic cells play a protective role during RSV infection by modulation of local immune responses.