Deciphering the Physiological Interaction between the Mosquito Immune and Circulatory Systems

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Mosquitoes fight infection by mounting powerful immune responses that are mediated by cells called hemocytes. Within the body cavity, or hemocoel, hemocytes either circulate with the hemolymph (insect blood) or exist as sessile cells (attached to tissues). Earlier experiments revealed that during the course of an infection, pathogens accumulate on the surface of the heart of adult mosquitoes. Examination of the pericardium then showed that a small population of sessile hemocytes exists in the regions that flank the valves of the heart (the periostial regions), and that these hemocytes readily phagocytose pathogens. Infection induces the recruitment of additional hemocytes to the periostial regions, and these hemocytes rapidly kill pathogens via phagocytosis, melanization and lysis. Currently there is a paucity of data on the effect of hemolymph circulation on immune responses, and on the role sessile hemocytes play in controlling infection. Thus, significant gaps exist in understanding the spatial and temporal dynamics of pathogen resistance in the insect hemocoel. This research will explore the biology of a newly discovered immune tissue in mosquitoes (periostial hemocytes) that fundamentally relies on the mechanics of the heart for pathogen killing. More specifically, this project will investigate the molecular, spatial, and temporal bases of infection-induced hemocyte aggregation on the surface of the insect heart. The project will yield critical insight into the anti-pathogen responses of insects, and will integrate this information into a broad conceptual framework on insect immunity, physiology, and development. Furthermore, this research will be carried out in mosquitoes, a socially and ecologically important insect group because of their role as pests and pathogen transmitters. Thus, data arising from this project could contribute to the development of novel pest and disease control strategies. In addition, the principal investigator will partner with Gower Elementary School (Metropolitan Nashville Public Schools) to introduce elementary school students to insect biology.This project has four primary objectives that collectively aim to decipher the physiological interaction between the mosquito immune and circulatory systems. Objective 1 will employ molecular and imaging methodologies to determine the pathways that drive the infection-induced migration of hemocytes to the surface of the heart. Objective 2 will rely on molecular and biochemical approaches to test whether during the course of an infection hemocyte-produced factors such as nitric oxide modulate cardiac physiology. Objective 3 will determine whether the interaction between the immune and circulatory systems is conserved during mosquito development. Specifically, because the general body plan as well as the flow of hemolymph are markedly different in the adult and larval life stages, objective 3 will employ organismal and imaging approaches to assess whether the immune and circulatory systems of larvae also interact during the course of an infection. If they do, the nature of that interaction will be defined. Finally, objective 4 will assess whether periostial hemocyte aggregation is a general feature by quantitatively measuring the occurrence of this response in a wide variety of insect species. It is expected that this research will uncover fundamental physiological interactions between the immune system and the circulatory system of insects.