Human skin Langerhans cells are targets of dengue virus infection

Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for which there is no antiviral treatment and no vaccine(1,2). Macrophages are important in dengue pathogenesis; however, the initial target cell for DV infection remains unknown. As DV is introduced into human skin by mosqui toes of the genus Aedes, we undertook experiments to determine whether huma n dendritic cells (DCs) were permissive for the growth of DV. Initial exper iments demonstrated that blood-derived DCs were 10-fold more permissive for DV infection than were monocytes or macrophages. We confirmed this with hu man skin DCs (Langerhans cells and dermal/interstitial DCs). Using cadaveri c human skin explants, we exposed skin DCs to DV ex vivo. Of the human leuk octye antigen DR-positive DCs that migrated from the skin, emigrants from b oth dermis and epidermis, 60-80% expressed DV antigens. These observations were supported by histologic findings from the skin rash of a human subject who received an attenuated tetravalent dengue vaccine. Immunohistochemistr y of the skin showed CD1a-positive DCs double-labeled with an antibody agai nst DV envelope glycoprotein. These data demonstrate that human skin DCs ar e permissive for DV infection, and provide a potential mechanism for the tr ansmission of DV into human skin.