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

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 Kit^W-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 Kit^W-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 Kit^W-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 Kit^W-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 Kit^W-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 Kit^W-sh/W-sh mice than in corresponding WT mice. In summary, compared with WT mice, Kit^W-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. [ABSTRACT FROM AUTHOR]