Complement-like proteins TEP1, TEP3 and TEP4 are positive regulators of periostial hemocyte aggregation in the mosquito Anopheles gambiae.

The mosquito immune and circulatory systems are functionally integrated. During an infection, hemocytes aggregate around the ostia (valves) of the dorsal vessel - areas of the heart called the periostial regions - where they phagocytose live and melanized pathogens. Although periostial hemocyte aggregation is an immune response that occurs following infection with bacteria and malaria parasites, the molecular basis of this process remains poorly understood. Here, we show that the thioester-containing proteins, TEP1, TEP3 and TEP4 are positive regulators of periostial hemocyte aggregation in the African malaria mosquito, Anopheles gambiae. RNAi-based knockdown of TEP1, TEP3 and TEP4 resulted in fewer periostial hemocytes following Escherichia coli infection, without affecting the adjacent population of non-periostial, sessile hemocytes. Moreover, knockdown of TEP1, TEP3 and TEP4 expression resulted in reduced bacterial accumulation and melanin deposition at the periostial regions. Finally, this study confirmed the role that TEP1 plays in reducing infection intensity in the hemocoel. Overall, this research shows that the complement-like proteins, TEP1, TEP3 and TEP4, are positive regulators of the functional integration between the immune and circulatory systems of mosquitoes.