Nasal virus infection induces asthma exacerbation through B-cell-dependent recruitment of inflammatory monocytes.

Abstract

Upper respiratory viral infections (URVIs) are responsible for 80% of asthma exacerbation episodes. However, the underlying mechanisms remain poorly understood. In this study, we used a mouse model of URVI and examined the impact of URVI on asthma phenotypes and the underlying mechanisms. Previously, we have reported that nasal-restricted infection with respiratory syncytial virus (RSV) only produces mild sino-nasal inflammation and mucus production, without causing direct lung infection. However, such nasal-restricted infection dramatically enhanced TH2 and TH17 inflammatory responses in the lungs and increased airway hyperresponsiveness (AHR) in mice with house dust mite (HDM)-induced asthma. Additionally, nasal-restricted infection with RSV recruited Ly6C+ inflammatory monocytes (IMs) into the lungs of mice with and without HDM-induced asthma. The expression of monocyte chemokines, including CCL2 and CCL7, also increased. Interestingly, nasal virus infection-induced AHR was abolished in mice depleted of IMs and in CCR2-/- mice, indicating that the recruited IMs play a key role in nasal virus infection-induced asthma exacerbations in mice. Lastly, we observed that recruitment of Ly6C+ IMs following URVI was abolished in mice lacking B cells and that nasal-restricted infection with RSV increased numbers of CCL2+CCL7+ B cells in the lungs of mice as compared to controls. Taken together, our data have shown that URVI enhances the allergic inflammatory response and AHR through a B cell‒monocyte regulatory axis.