The Upper Respiratory Tract Exhibits Reduced Interferon Response that Contributes to Limited CD8 +T Cell Recruitment and Delayed Clearance of Human Metapneumovirus

Abstract Human metapneumovirus (HMPV) is a leading cause of acute upper and lower respiratory infections. Although nearly everyone infected during early childhood, re-infections occur often, highlighting difficulty in building long-term immunity. We employed mouse model HMPV infection to elucidate differences tract immune responses, address why airway does not establish durable protective found burden was higher nasal airways exhibited delayed clearance compared lung. Additionally, there low expression antiviral interferons (IFN) inflammatory cytokines. Key innate cells, including macrophages, monocytes, dendritic were present the nose at baseline but upregulated by infection. previously showed HMPV-specific lung CD8 +T cells (T CD8) are impaired, exhibiting sustained high PD-1 levels reduced functionality. Despite viral load, few T CD8and they did exhibit impairment. To test whether IFN led this phenotype, we administered type I an airway-restricted fashion post-infection. This titers, increased cell number, expression, functionality CD8. subdued response, intranasal vaccination with small-volume dose elicited modest reduction titers on challenge no improvement clinical disease. Our findings reveal quiescent landscape despite that contributed slow modulated, part, expression. Supported NIH R01 AI085062-06 (JVW), T32 AI138954-4 (JS), UPMC Children's Hospital Pittsburgh Research Advisory Council Graduate Fellowship (JS).