Distinct innate signaling and activation of dendritic cells during the neonatal period determines their functional response to respiratory syncytial virus infection

• Published in: The Journal of immunology (1950) Vol. 198; no. 1_Supplement; pp. 203 - 203.4
• Main Authors: Lau-Kilby, Annie W, Kehl, Margaret, Malloy, Allison MW
• Format: Journal Article
• Language: English
• Published: 01-05-2017
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.203.4

Dendritic cells (DCs) are among the first to respond to infection, providing the critical link between innate and adaptive immunity. Neonates often have weak innate immune responses that can limit adaptive immunity and contribute to increased susceptibility and more severe infection with intracellular pathogens, such as respiratory syncytial virus (RSV). We have previously shown differential migration and defective activation of neonatal murine respiratory CD103+ DCs, which is associated with diminished RSV-specific CD8 T cell responses in neonatal mice. In order to define the age-dependent regulation of respiratory DC function, we have developed a neonatal mouse model of RSV to track antigen presentation via infection with an ovalbumin-expressing RSV and an antibody against H2kb-OVA257–264. We found adequate transfer of RSV-derived OVA257–264 by neonatal CD103+ DCs to the dLN, suggesting poor CD8 T cell responses are not due to limited antigen presentation. However, neonatal CD103+ DCs expressing H2kb-OVA257–264 failed to upregulate CD80/86, which is critical to T cell stimulation. RNA-seq analysis of H2kb-OVA257–264+ CD103+ DCs implicated defective type I IFN signaling in neonates that may influence reduced activation. In support of this, while we find type I IFN to be diminished in the neonatal lung, treatment of neonates with IFN-α failed to restore the activation of neonatal H2kb-OVA257–264+ CD103+DCs.
Our data demonstrate a distinct developmental regulation of innate immunity in early life and identify type I IFN signaling as contributing to defective DC activation during RSV infection in neonates. Defining age-dependent mechanisms controlling immunity may lead to intelligently designed vaccines for this age group.