No study has investigated the participation of Ly6C+ monocytes in the earliest phase of skin infection with the mosquito-borne West Nile virus. In a novel murine model mimicking natural dermal infection, CCL2-dependent bone marrow (BM)-derived monocyte migration, differentiation into Ly6C+ dendritic cells (DC), and accumulation around dermal deposits of infected fibroblasts by day 1 postinfection were associated with increasing numbers of monocyte-derived TNF/inducible NO synthase-producing DC by day 2 postinfection in draining auricular lymph nodes (ALN). Adoptive transfer demonstrated simultaneous migration of bone marrow-derived Ly6Clo monocytes to virus-infected dermis and ALN, where they first become Ly6Chi DC within 24 h and then Ly6Clo DC by 72 h. DC migration from the infected dermis to the ALN derived exclusively from Ly6Clo BM monocytes. This demonstrates that Ly6Chi and Ly6Clo BM-derived monocytes have different fates in vivo and suggests that BM may be a reservoir of preinflammatory monocytes for rapid deployment as inflammatory DC during virus infection.

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