Selective susceptibility of human skin antigen presenting cells to productive dengue virus infection

PLoS Pathog. 2014 Dec 4;10(12):e1004548. doi: 10.1371/journal.ppat.1004548. eCollection 2014 Dec.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dengue Virus / immunology*
  • Dengue* / immunology
  • Dengue* / pathology
  • Humans
  • Langerhans Cells* / immunology
  • Langerhans Cells* / pathology
  • Langerhans Cells* / virology
  • Macrophages / immunology
  • Macrophages / pathology
  • Macrophages / virology
  • Mice
  • Mice, Knockout

Grant support

This work was supported by the Agency for Science, Technology and Research, (A*STAR), Singapore. DC is a recipient of the Singapore International Graduate Award (SINGA) and was funded by the A*STAR Graduate Academy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.