Deciphering the Physiological Interaction between the Mosquito Immune and Circulatory Systems

蚊子通过增强由血细胞介导的强大免疫反应来对抗感染。 在体腔或血腔中，血细胞要么与血淋巴（昆虫血液）一起循环，要么作为固着细胞（附着在组织上）存在。 早期的实验表明，在感染过程中，病原体会积聚在成年蚊子的心脏表面。 对心包的检查表明，在心脏瓣膜两侧的区域（口周区域）存在少量无柄血细胞，并且这些血细胞容易吞噬病原体。 感染诱导额外的血细胞募集到口周区域，并且这些血细胞通过吞噬作用、黑化和溶解作用快速杀死病原体。 目前，关于血淋巴循环对免疫反应的影响以及固着血细胞在控制感染中的作用的数据还很少。 因此，在理解昆虫血腔中病原体抗性的空间和时间动态方面存在重大差距。 这项研究将探索一种新发现的蚊子免疫组织（口周血细胞）的生物学，这种免疫组织从根本上依赖于心脏杀死病原体的机制。 更具体地说，本项目将调查感染诱导的血细胞聚集在昆虫心脏表面的分子，空间和时间基础。 该项目将对昆虫的抗病原体反应产生重要的见解，并将这些信息整合到昆虫免疫，生理和发育的广泛概念框架中。 此外，这项研究将在蚊子中进行，蚊子是一种具有社会和生态重要性的昆虫群体，因为它们是害虫和病原体传播者。 因此，该项目产生的数据可能有助于制定新的病虫害控制战略。此外，首席研究员将与高尔小学（大都会纳什维尔公立学校）合作，向小学生介绍昆虫生物学。该项目有四个主要目标，共同旨在破译蚊子免疫和循环系统之间的生理相互作用。 目标1将采用分子和成像方法来确定感染诱导的血细胞迁移到心脏表面的途径。 目标2将依赖于分子和生物化学方法来测试在感染过程中血细胞产生的因子如一氧化氮是否调节心脏生理学。 目的3将确定免疫和循环系统之间的相互作用是否在蚊子发育过程中是保守的。 具体来说，由于成虫和幼虫生命阶段的总体身体结构以及血淋巴流动显着不同，目标3将采用生物体和成像方法来评估幼虫的免疫和循环系统是否也在感染过程中相互作用。 如果他们这样做，这种相互作用的性质将被定义。 最后，目标4将通过定量测量各种昆虫物种中这种反应的发生率来评估孔周血细胞聚集是否是一个一般特征。 预计这项研究将揭示昆虫免疫系统和循环系统之间的基本生理相互作用。

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.