Differential antigen presentation and transport by neonatal and adult dendritic cell subsets during Respiratory Syncytial Virus (RSV) infection

Abstract

Abstract Dendritic cells (DCs) are critical for the induction of anti-viral CD8+ T cells. Young infants mount poor antiviral responses contributing to increased disease susceptibility and severity compared with acquisition later in life. Using a mouse model of respiratory syncytial virus (RSV), we have previously shown differences in the number of DCs that can carry antigen from the lung to the lung-draining lymph node (dLN) during infection between adults and neonates, and this is associated with age-dependent differences in RSV-specific CD8+ T cell responses. However whether adult or neonatal DCs more readily present antigen for T cell engagement is unknown. In this study, we used an ovalbumin-expressing RSV (RSV-OVA) to track antigen presentation through early infection. In the lung, expression of MHCI-bound OVA (MHCI-OVA) was highest on adult CD103+ DCs; while in the dLN a greater number of neonatal CD103+ DCs expressed MHCI-OVA. Quantification of the migration-associated chemokine receptor 7 identified increased expression on neonatal MHCI-OVA-expressing CD103+ DCs compared to adults, suggesting adults may more readily present antigen but neonatal CD103+ DCs were more apt to migrate upon antigen acquisition. However, neonates failed to induce an OVA-specific T cell response in the lung in contrast to adults. Together our data indicate that in neonates MHCI-OVA+ CD103+ DCs were more proficient at migration resulting in a greater number of MHCI-OVA-presenting CD103+ DCs in the dLN;- however, they failed to induce an OVA-specific T cell response. Thus antigen abundance was not the primary determinant of CD8+ T cell induction during RSV infection in neonates, suggesting that alternate mechanism(s) limit their DC-mediated T cell responses.