Anopheles responses to Plasmodium infected blood

描述（由申请人提供）：冈比亚按蚊转基因和高通量基因组技术的最新进展使其成为研究宿主-寄生虫相互作用和先天免疫的强大模式生物。此外，按蚊传播人类最严重的疾病之一，疟疾。缺乏有效的疫苗、寄生虫对药物产生抗药性以及蚊子对杀虫剂产生抗药性，这些都助长了这种疾病的蔓延，因此迫切需要制定新的防治战略。基于阻断疟原虫在媒介蚊子中的生命周期的控制策略将需要理解蚊子-寄生虫相互作用中涉及的分子机制。蚊子的先天免疫系统能够杀死大量的疟疾寄生虫。摄入疟疾感染的血液导致先天免疫应答的激活，这显著有助于杀死中肠中的疟原虫。这些免疫反应的特异性激发子、它们调节的免疫途径及其对寄生虫不同阶段的杀疟原虫活性尚不清楚。该应用将利用全基因组微阵列对与疟疾感染的血液相关的不同组分（激发子）的全身和中肠特异性转录物应答进行全面解剖，然后评估这些应答对疟原虫发育的影响。这些分析将阐明蚊子的感染反应生理学的重要方面，并提供抗疟原虫免疫反应的调节信息。这项研究将为蚊子的先天免疫系统在制定疟疾控制策略方面的应用提供基线评估。

DESCRIPTION (provided by applicant): Recent advances in Anopheles gambiae transgenic and high throughput genomic technologies have rendered it a powerful model organism for the study of host - parasite interactions and innate immunity. In addition, Anopheline mosquitoes transmit one of the most serious diseases of mankind, malaria. The lack of effective vaccines, the development of parasite resistance to drugs and mosquito resistance to insecticides contribute to the expansion of the disease and have thereby created an acute need for the development of additional novel control strategies. Control strategies based on the blocking of Plasmodium's lifecycle in the vector mosquito will require the understanding of the molecular mechanisms implicated in mosquito - parasite interactions. The mosquito's innate immune system is capable of killing large numbers of malaria parasites. Ingestion of malaria infected blood results in the activation of innate immune responses that contribute significantly to the killing of Plasmodia in the midgut. The specific elicitors of these immune responses, the immune pathways they regulate and their plasmodiocidal activity on the different stages of the parasite are as yet unknown. This application will utilize a full genome microarray for a comprehensive dissection of the systemic and midgut specific transcript responses to the different components (elicitors) that are associated with malaria infected blood and then assess the impact of these responses on Plasmodium development. These analyses will elucidate important aspects of the mosquito's infection responsive physiology and provide information on the regulation of antiplasmodial immune response. It will provide baseline assessment on the utilization of the mosquito's innate immune system for the development of malaria control strategies.