Immune responses to dengue virus in the skin

Dengue virus (DENV) causes infection in humans and current estimates place 40% of the world population at risk for contracting disease. There are four DENV serotypes that induce a febrile illness, which can develop into a severe and life-threatening disease in some cases, characterized primarily by vascular dysregulation. As a mosquito-borne infection, the skin is the initial site of DENV inoculation and also where primary host immune responses are initiated. This review discusses the early immune response to DENV in the skin by both infection target cells such as dendritic cells and by immune sentinels such as mast cells. We provide an overview of the mechanisms of immune sensing and functional immune responses that have been shown to aid clearance of DENV in vivo. Finally, we discuss factors that can influence the immune response to DENV in the skin, such as mosquito saliva, which is co-injected with virus during natural route infection, and pre-existing immunity to other DENV serotypes or to related flaviviruses.