Mast cell-macrophage dynamics in modulation of dengue virus infection in skin

Ya Ting Chu, Shu Wen Wan, Robert Anderson, Yee Shin Lin

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Dengue virus (DENV) infection causes dengue fever, dengue haemorrhagic fever, or dengue shock syndrome. Mast cells have been speculated to play a role in DENV disease although their precise roles are unclear. In this study, we used mast cell-deficient KitW-sh/W-sh mice to investigate the involvement of mast cells after intradermal DENV infection. An approximately two- to three-fold higher level of DENV NS3 antigen was detected at the skin inoculation site in DENV-infected KitW-sh/W-sh mice than in DENV-infected wild-type (WT) mice (using a dose of 1 × 109 plaque-forming units/mouse). Moreover, as an indicator of heightened pathogenesis, a more prolonged bleeding time was observed in DENV-infected KitW-sh/W-sh mice than in WT mice. Monocytes/macrophages are considered to be important targets for DENV infection, so we investigated the susceptibility and chemokine response of DENV-infected peritoneal macrophages from KitW-sh/W-sh and WT mice both ex vivo and in vivo. There was a tendency for higher DENV infection and higher secretion of CCL2 (MCP-1) from peritoneal macrophages isolated from KitW-sh/W-sh mice than those from WT mice. In vivo studies using intradermal inoculation of DENV showed about twofold higher levels of infiltrating macrophages and CCL2 (MCP-1) at the inoculation site in both mock control and DENV-inoculated KitW-sh/W-sh mice than in corresponding WT mice. In summary, compared with WT mice, KitW-sh/W-sh mice show enhanced DENV infection and macrophage infiltration at the skin inoculation site as well as increased DENV-associated bleeding time. The results indicate an intriguing interplay between mast cells and tissue macrophages to restrict DENV replication in the skin.

Original languageEnglish
Pages (from-to)163-172
Number of pages10
JournalImmunology
Volume146
Issue number1
DOIs
Publication statusPublished - 2015 Sep 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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