Search

Influenza A virus-specific (IAV-specific) T cell responses are important correlates of protection during primary and subsequent infections. The generation and maintenance of robust IAV-specific T cell responses relies on T cell interactions with dendritic cells (DCs). In this study, we explore the role of the nucleotide-binding domain leucine-rich repeat- containing receptor family member NLRC4 in modulating the DC phenotype during IAV infection. [Nlrc4.sup.-/-] mice had worsened survival and increased viral titers during infection, normal innate immune cell recruitment, and IAV-specific [CD8.sup.+] T cell responses, but severely blunted IAV-specific [CD4.sup.+] T cell responses compared with WT mice. The defect in the pulmonary IAV-specific [CD4.sup.+] T cell response was not a result of defective priming or migration of these cells in [Nlrc4.sup.-/-] mice but was instead due to an increase in [FasL.sup.+] DCs, resulting in IAV- specific [CD4.sup.+] T cell death. Together, our data support a role for NLRC4 in regulating the phenotype of lung DCs during a respiratory viral infection and thereby influencing the magnitude of protective T cell responses., Introduction Influenza A virus (IAV) is a respiratory pathogen responsible for seasonal epidemics that can cause severe disease and death, most commonly in the very young, very old, and immunocompromised [...]