Interleukin-10 limits RSV-induced disease severity by modulating the virus-specific T cell response (105.4)

Abstract

Abstract The host immune response contributes to the severity of pulmonary disease following acute respiratory syncytial virus (RSV) infection. IL-10 is a potent immunomodulatory cytokine produced by multiple CD4 T cell subsets following RSV infection. We hypothesized that IL-10 negatively regulates the RSV-specific immune response thereby limiting disease severity. We observed that peak viral replication and clearance is not altered by the absence of IL-10 or following IL-10R blockade. However, disease severity as measured by weight loss and airway resistance is significantly increased in the absence of IL-10 or following IL-10R blockade following acute RSV infection. Histological analysis indicates that following IL-10R blockade there is an increase in mucus production and inflammation in the lung airways. We also observed a significant increase in pro-inflammatory cytokines and chemokines in the absence of IL-10 following RSV infection. Moreover, the total number of the IFN-γ-producing CD8 and CD4 T cells responding to the infection are significantly increased following IL-10R blockade. Interestingly, IL-10R blockade during RSV infection also altered CD4 T cell subset distribution, resulting in a significant increase in IL-17A-producing CD4 T cells and a concomitant decrease in Foxp3+ regulatory T cells. These results demonstrate that IL-10 plays a critical role in modulating the adaptive immune response to RSV by limiting T-cell-mediated pulmonary inflammation and injury.