Dendritic cells and dengue virus infection in the skin: immune response and the role of mosquito saliva

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Dengue virus is transmitted via the bite of infected Aedes aegypti and Ae. albopictus mosquitoes and causes the most prevalent arthropod-borne viral disease of humans, with 40 million cases per year. The disease is spread in tropical areas of South and Southeast Asia, Central & South America, and parts of Africa. Dengue virus infection is often asymptomatic, but can induce dengue fever, characterized by symptoms resembling a common cold, such as fever, headache, muscle and joint pains. In rare cases it can lead to dengue hemorrhagic fever and shock syndrome and can be fatal. Dendritic cells (DCs) reside in the skin and serve as guards of the immune system. Upon invasion of a pathogen, DCs become activated, secrete inflammatory cytokines, migrate to lymph nodes, and induce adaptive immune responses. In contrast, DCs are infected by dengue virus and may potentially contribute to its spread. Little is known about the early events after the transmission of dengue virus in the skin and how the infection spreads throughout the body to cause the disease. This research aims on understanding the early events of dengue virus infection of the skin and the immune response that is induced. In a newly developed mouse model, the ear skin is inoculated with dengue virus intradermally. One or two days later, cells of the skin and lymph nodes are analyzed. Therefore, proteins that are characteristic for certain cell populations (e.g. DCs) as well as dengue virus proteins are stained via specific antibodies to identify infected cell types. The samples are then analyzed via flow cytometry (FACS). Also, the presence of saliva from the mosquitoes may influence the infection of DCs with dengue virus early after transmission. This may affect the immune response and the course of infection. Studying these aspects of early dengue virus infection will provide the basis to better define future vaccine strategies blocking dengue virus spread in the skin early after transmission.