Effects of Blood Meal on Cellular Immunity in Mosquitoes

描述（由申请人提供）：疟疾仍然是一个全球性的健康问题，其中蚊子冈比亚按蚊s.s.是恶性疟原虫的主要传播媒介研究蚊子的免疫力非常重要，因为从这些研究中获得的知识可以应用于未来消除疟疾疾病传播周期的方法。蚊子免疫的一个主要方面是由血细胞提供的细胞应答。其重要性的相关性来自TEP-1和LRIM 1的报道，它们（1）仅在血细胞中产生，并且（2）对于疟疾寄生虫清除至关重要。这项提案将研究吸血后调节蚊子血细胞稳态的分子机制，以及这对蚊子对疟疾寄生虫的免疫力有什么影响。长期目标是了解蚊子细胞免疫的动态及其在病原体传播中的作用。具体目的是（1）确定血餐后血细胞增殖的分子机制，（2）确定血餐诱导的血细胞增殖后血细胞被清除的分子机制，和（3）确定血细胞稳态对免疫的作用。为了确定是什么调节血细胞稳态，将采用感兴趣的途径的反向遗传学和测量血细胞丰度的定量测定。为了确定血细胞稳态对免疫的作用，将在血餐后血细胞中改变的信号传导的反向遗传背景中确定伯氏疟原虫感染强度。在完成这些研究目标后，将确定负责调节血餐后血细胞数量的分子机制，并阐明其对蚊子免疫力的影响。重要的是，这项研究将建立新的方法和模式，在昆虫的细胞免疫可能适用于其他媒介传播的疾病。这一建议的健康相关性是血细胞在疟疾寄生虫清除中的重要性，以及当血液餐后循环血细胞数量增加时蚊子的明显益处。

DESCRIPTION (provided by applicant): Malaria continues to be a global health problem where the mosquito Anopheles gambiae s.s. serves as a major vector for Plasmodium falciparum. Studying mosquito immunity is of grave importance because knowledge gained from these studies can be applied to future methods of abolishing the disease transmission cycle of malaria. One main aspect of mosquito immunity is the cellular response provided by hemocytes. Relevance of their importance comes from reports of TEP-1 and LRIM1, which are (1) produced solely in hemocytes and (2) are vital for malaria parasite clearance. This proposal will study molecular mechanisms behind regulating mosquito hemocyte homeostasis after a blood meal, and what affect this has on mosquito immunity to malaria parasites. The long-term goal is to understand the dynamics of cellular immunity in mosquitoes and its role in pathogen transmission. The specific aims are (1) determine a molecular mechanism of hemocyte proliferation after a blood meal, (2) determine a molecular mechanism through which hemocytes are cleared after blood meal-induced hemocyte proliferation, and (3) determine what role hemocyte homeostasis has on immunity. To determine what regulates hemocyte homeostasis, reverse genetics of pathways of interest and quantitative assays measuring hemocyte abundance will be employed. To determine what role hemocyte homeostasis has on immunity, Plasmodium berghei infection intensities will be determined in reverse genetic backgrounds of altered signaling in hemocytes after blood meal. Upon completion of these research goals, the molecular mechanisms responsible for regulating hemocyte numbers after a blood meal will be determined and their consequences on mosquito immunity elucidated. Importantly, this study will establish novel methodologies and paradigms for cellular immunity in insects that are likely to be applicable to other vector-borne diseases. The health relevance of this proposal is the importance of hemocytes in malaria parasite clearance, and the obvious benefits the mosquito has when the number of circulating hemocytes increases after blood meal.