A Role for Human Skin Mast Cells in Dengue Virus Infection and Systemic Spread

Dengue virus (DENY) is a mosquito-borne flavivirus that causes serious global human disease and mortality. Skin immune cells are an important component of initial DENY infection and systemic spread. Here, we show that mast cells are a target of DENY in human skin and that DENY infection of skin mast cells induces degranulation and alters cytokine and growth factor expression profiles. Importantly, to our knowledge, we also demonstrate for the first time that DENY localizes within secretory granules in infected skin mast cells. In addition, DENY within extracellular granules was infectious in vitro and in vivo, trafficking through lymph to draining lymph nodes in mice. We demonstrate an important role for human skin mast cells in DENY infection and identify a novel mechanism for systemic spread of DENY infection from the initial peripheral mosquito injection site.