Figure 7. Model: Unique I-IFNs responses determine the functional fate of migratory lung DCs during respiratory virus infection.

A. CD103⁺ DCs are naturally resistant to IFNAR signaling and allow virus replication to higher levels leading to enhanced antigen presentation, when compared to CD11b^high DCs that respond strongly to I-IFNs and impede virus replication and Ag presentation. B. The in vivo implications of virus infection and unique IFNAR signaling by CD103⁺ DCs and CD11b^high DCs during influenza virus infection and other respiratory viruses. Both lung DCs begin to migrate to the MLNs when lung inflammation is initiated around 2 days post-infection, an event that is preceded by unabated virus replication without an apparent innate response (stealth phase). IFNAR signaling is not protective in CD103⁺ DCs and their inherent susceptibility to virus infection may make them function as “Trojan horses” that transfer virus to other leukocytes in the MLNs and upon exit through efferent lymphatics disseminate virus systemically.