Selective Susceptibility of Human Skin Antigen Presenting Cells to Productive Dengue Virus Infection

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Dengue virus (DENV) is transmitted by mosquitoes with skin as point of entry for the virus. Here, we investigated DENV infection in primary human skin cells and their initial immune response. Using skin from normal human donors for infection with DENV in vitro we identified antigen-presenting cells (APCs) as main targets of DENV. Further analysis showed that only distinct subsets of dendritic cells (DCs) and macrophages were infected and efficiently produced viral progeny. Langerhans cells were most susceptible to infection despite lacking DC-SIGN, a previously described DENV receptor. Infection of the other DC subsets and macrophages was also independent of DC-SIGN expression. Genes of the interferon pathway and CCL5, a chemokine attracting immune cells to sites of inflammation, were highly up-regulated in the infected DC subsets. Using a mouse infection model, we showed that murine dermal DCs were also susceptible to DENV and migrated to draining lymph nodes. At the same time infiltrating monocytes differentiated into monocyte-derived cells at the site of infection and became an additional target for DENV in vivo. These data demonstrate that DENV differentially infects and activates primary human skin APCs and that infected cell types individually contribute to inflammation and the adaptive response.

Vyšlo v časopise: Selective Susceptibility of Human Skin Antigen Presenting Cells to Productive Dengue Virus Infection. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004548
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004548

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