title: Selective susceptibility of human skin antigen presenting cells to productive dengue virus infection.
abstract: Dengue is a growing global concern with 390 million people infected each year. Dengue virus (DENV) is transmitted by mosquitoes, thus host cells in the skin are the first point of contact with the virus. Human skin contains several populations of antigen-presenting cells which could drive the immune response to DENV in vivo: epidermal Langerhans cells (LCs), three populations of dermal dendritic cells (DCs), and macrophages. Using samples of normal human skin we detected productive infection of CD14(+) and CD1c(+) DCs, LCs and dermal macrophages, which was independent of DC-SIGN expression. LCs produced the highest viral titers and were less sensitive to IFN-β. Nanostring gene expression data showed significant up-regulation of IFN-β, STAT-1 and CCL5 upon viral exposure in susceptible DC populations. In mice infected intra-dermally with DENV we detected parallel populations of infected DCs originating from the dermis and migrating to the skin-draining lymph nodes. Therefore dermal DCs may simultaneously facilitate systemic spread of DENV and initiate the adaptive anti-viral immune response.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cerny
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Muzlifah
authors.initials: M
authors.lastname: Haniffa
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Amanda
authors.initials: A
authors.lastname: Shin
authors.affiliation: Institute of Molecular Biology, Agency for Science, Technology and Research, Singapore; Division of Rheumatology, University Medicine Cluster, National University Health System, Singapore.
authors.forename: Paul
authors.initials: P
authors.lastname: Bigliardi
authors.affiliation: Department of Plastic Surgery, Singapore General Hospital, Singapore.
authors.forename: Bien Keem
authors.initials: BK
authors.lastname: Tan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Bernett
authors.initials: B
authors.lastname: Lee
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Department of General Surgery, Tan Tock Seng Hospital, Singapore.
authors.forename: Ern Yu
authors.initials: EY
authors.lastname: Tan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Katja
authors.initials: K
authors.lastname: Fink
mesh_terms: D000818:Animals; D003715:Dengue / Q000276:immunology / Q000473:pathology; D003716:Dengue Virus / Q000276:immunology*; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout