MAVS plays an essential role in host immunity against human metapneumovirus (MUC1P.907)

Abstract

Abstract Human metapneumovirus (hMPV) is a common cause of respiratory tract infection in the pediatrics population. Recently, we and others have shown RIG-I-like receptors are essential for hMPV-induced cellular antiviral signaling. However, the contribution of those receptors in host immunity against pulmonary hMPV infection is largely unexplored. In this study, mice deficient in MAVS, an adaptor of RIG-I-like receptors, was used to investigate the role(s) of these receptors in pulmonary responses to hMPV infection. MAVS deletion significantly impaired the induction of IFN-I and other proinflammatory cytokines by hMPV. Compared to wild type mice, mice lacking MAVS harbored a higher viral load and demonstrated impaired abilities to activate pulmonary dendritic cells (DCs), subsequently leading to abnormal memory T cell responses to hMPV infection. In addition, we found that MAVS is required for the recruitment of DCs and other immune cells to the bronchoalveolar lavage fluid (BALF). Taken together, our data indicate that MAVS-mediated pathways are essential for the pulmonary immune responses, both innate and adaptive, to hMPV infection.