title: Human skin Langerhans cells are targets of dengue virus infection.
abstract: Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for which there is no antiviral treatment and no vaccine. Macrophages are important in dengue pathogenesis; however, the initial target cell for DV infection remains unknown. As DV is introduced into human skin by mosquitoes of the genus Aedes, we undertook experiments to determine whether human dendritic cells (DCs) were permissive for the growth of DV. Initial experiments demonstrated that blood-derived DCs were 10-fold more permissive for DV infection than were monocytes or macrophages. We confirmed this with human skin DCs (Langerhans cells and dermal/interstitial DCs). Using cadaveric human skin explants, we exposed skin DCs to DV ex vivo. Of the human leukocyte antigen DR-positive DCs that migrated from the skin, emigrants from both 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. Immunohistochemistry of the skin showed CD1a-positive DCs double-labeled with an antibody against DV envelope glycoprotein. These data demonstrate that human skin DCs are permissive for DV infection, and provide a potential mechanism for the transmission of DV into human skin.
authors.affiliation: Viral and Rickettsial Diseases Department, Naval Medical Research Center, Bethesda, Maryland 20889-5607, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Wu
authors.forename: G
authors.initials: G
authors.lastname: Grouard-Vogel
authors.forename: W
authors.initials: W
authors.lastname: Sun
authors.forename: J R
authors.initials: JR
authors.lastname: Mascola
authors.forename: E
authors.initials: E
authors.lastname: Brachtel
authors.forename: R
authors.initials: R
authors.lastname: Putvatana
authors.forename: M K
authors.initials: MK
authors.lastname: Louder
authors.forename: L
authors.initials: L
authors.lastname: Filgueira
authors.forename: M A
authors.initials: MA
authors.lastname: Marovich
authors.forename: H K
authors.initials: HK
authors.lastname: Wong
authors.forename: A
authors.initials: A
authors.lastname: Blauvelt
authors.forename: G S
authors.initials: GS
authors.lastname: Murphy
authors.forename: M L
authors.initials: ML
authors.lastname: Robb
authors.forename: B L
authors.initials: BL
authors.lastname: Innes
authors.forename: D L
authors.initials: DL
authors.lastname: Birx
authors.forename: C G
authors.initials: CG
authors.lastname: Hayes
authors.forename: S S
authors.initials: SS
authors.lastname: Frankel
mesh_terms: D001773:Blood Cells / Q000821:virology; D003716:Dengue Virus / Q000254:growth & development*; D020405:Dermis / Q000821:virology; D005076:Exanthema; D006801:Humans; D007801:Langerhans Cells / Q000821:virology*; D008264:Macrophages / Q000821:virology; D009000:Monocytes / Q000821:virology; D012867:Skin / Q000166:cytology / Q000821:virology*; D014764:Viral Proteins / Q000302:isolation & purification; D014765:Viral Vaccines / Q000009:adverse effects
chemical_list: D014764:Viral Proteins; D014765:Viral Vaccines