Langerhans Cells Orchestrate the Protective Antiviral Innate Immune Response in the Lymph Node.

During disseminating viral infections, a swift innate immune response (IIR) in the draining lymph node (dLN) that restricts systemic viral spread is critical for optimal resistance to disease. However, it is unclear how this IIR is orchestrated. We show that after footpad infection of mice with ectromelia virus, dendritic cells (DCs) highly expressing major histocompatibility complex class II (MHC class II DCs), including CD207 epidermal Langerhans cells (LCs), CD103CD207 double-positive dermal DCs (DP-DCs), and CD103CD207 double-negative dermal DCs (DN-DCs) migrate to the dLN from the skin carrying virus. MHC class II DCs, predominantly LCs and DP-DCs, are the first cells upregulating IIR cytokines in the dLN. Preventing MHC class II DC migration or depletion of LCs, but not DP-DC deficiency, suppresses the IIR in the dLN and results in high viral lethality. Therefore, LCs are the architects of an early IIR in the dLN that is critical for optimal resistance to a disseminating viral infection.