Tools to Decipher Vector-Borne Pathogen and Host Interactions in the Skin

Several pathogens transmitted by hematophagous vectors are inoculated in the host skin during an infective bite. Viruses, bacteria, and parasites stay at the inoculation site from minutes to days until disseminating throughout the host. Notably, early excision of the bite site profoundly inhibits host infection, indicating that most, if not all, pathogens are deposited together with saliva in the extravascular regions of the host skin. This delayed migration is a hallmark of this initial, and little explored, skin phase of infection, which is further characterized by the dynamic interaction of vector saliva components, the vector-borne pathogens, and resident and immune host cells. Here, we emphasize the commonality of this skin phase in the life history of pathogens transmitted by hematophagous vectors and present some tools to decipher host-pathogen interactions in this cutaneous environment. In the first part of the chapter, we focus on the effectiveness of in vivo imaging to characterize and functionally analyze this skin phase using a rodent malaria model. In the second part, we exploit the utilization of skin explants and primary cell culture to further investigate the cellular and molecular mechanisms of infection and persistence of various vector-borne pathogens in the human skin. Finally, we discuss the possibility of combining these two approaches aiming at the direct and unprecedented observation of the in vivo behavior of vector-borne pathogens in the human skin explants engrafted in humanized mice.