Respiratory Syncytial Virus-Induced Activation and Migration of Respiratory Dendritic Cells and Subsequent Antigen Presentation in the Lung-Draining Lymph Node

In the respiratory tract, different dendritic cell (DC) populations guard a tight balance between tolerance and immunity to infectious or harmless materials to which the airways are continuously exposed. For infectious and noninfectious antigens administered via different routes, different subsets of DC might contribute during the induction of T-cell tolerance and immunity. We studied the impact of primary respiratory syncytial virus (RSV) infection on respiratory DC composition in C57BL/6 mice. We also tracked the migration of respiratory DC to the lymph nodes and studied antigen presentation by lung-derived and lymph node-resident DC to CD4(+) and CD8(+) T cells. We observed a massive influx of mainly CD103(-) CD11b(high) CD11c(+) conventional DC (cDC) and plasmacytoid DC during the first 7 days of RSV infection, while CD103(+) CD11b(low) CD11c(+) cDC disappeared from the lung. The two major subsets of lung tissue DC, CD103(+) CD11b(low) CD11c(+) and CD103(-) CD11b(high) CD11c(+) cDC, both transported RSV RNA to the lung-draining lymph node. Furthermore, these lung-derived cDC subsets as well as resident LN DC, which did not contain viral RNA, displayed viral antigen by major histocompatibility complex class I and class II to CD8(+) and CD4(+) T cells. Taken together, our data indicate that during RSV infections, at least three DC subsets might be involved during the activation of lymph node-homing naive and memory CD4(+) and CD8(+) T cells.