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

登革热病毒通过受感染的埃及伊蚊和伊蚊叮咬传播。白纹伊蚊是人类最常见的节肢动物传播的病毒性疾病，每年有4000万例病例。该病在南亚和东南亚的热带地区、中美洲和南美洲以及非洲部分地区传播。登革热病毒感染通常无症状，但可诱发登革热，其特征是类似普通感冒的症状，如发烧、头痛、肌肉和关节疼痛。在极少数情况下，它会导致登革热出血热和休克综合征，并可能是致命的。树突状细胞（dc）存在于皮肤中，充当免疫系统的守卫者。当病原体入侵时，树突状细胞被激活，分泌炎性细胞因子，迁移到淋巴结，并诱导适应性免疫反应。相反，树突状病毒感染登革热病毒，并可能促进其传播。人们对登革热病毒在皮肤中传播后的早期事件以及感染如何在全身传播从而导致该病知之甚少。本研究旨在了解登革热病毒感染皮肤的早期事件和由此引起的免疫反应。在新开发的小鼠模型中，耳部皮肤皮内接种登革病毒。1 ~ 2天后，对皮肤细胞和淋巴结进行分析。因此，通过特异性抗体对某些细胞群（如dc）的特征蛋白以及登革热病毒蛋白进行染色，以识别受感染的细胞类型。然后通过流式细胞术（FACS）分析样品。此外，蚊子唾液的存在可能在传播后早期影响dc与登革热病毒的感染。这可能会影响免疫反应和感染过程。研究登革热病毒早期感染的这些方面将为更好地确定未来阻断登革热病毒传播后早期在皮肤中传播的疫苗策略提供基础。

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.