Accelerated dendritic cell differentiation from migrating Ly6C(lo) bone marrow monocytes in early dermal West Nile virus infection.
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 Ly6C(lo) monocytes to virus-infected dermis and ALN, where they first become Ly6C(hi) DC within 24 h and then Ly6C(lo) DC by 72 h. DC migration from the infected dermis to the ALN derived exclusively from Ly6C(lo) BM monocytes. This demonstrates that Ly6C(hi) and Ly6C(lo) 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.
Discipline of Pathology, School of Medical Sciences, Bosch Institute, University of Sydney, Sydney, New South Wales 2006, Australia.
Ariane M
AM
Davison
Nicholas J C
NJ
King
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012874:Skin Diseases, Infectious / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013997:Time Factors; D014709:Vero Cells; D014901:West Nile Fever / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014902:West Nile virus / Q000276:immunology
D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse