Endocrine regulation of immunity and reproduction in mosquitoes

蚊子是非常重要的昆虫，因为大多数物种都以脊椎动物的血液为食来繁殖。 吸血也是为什么一些蚊子传播疟疾寄生虫和寨卡病毒等微生物的原因，这些微生物可能会导致人类严重疾病。 激素是在不同器官、组织和细胞之间协调功能的分子。 先前的研究涉及特定的激素调节蚊子繁殖和免疫防御致病微生物，但所涉及的分子机制在很大程度上是未知的。 该项目将确定吸血后激素在蚊子体内激活的免疫反应，这些免疫反应如何影响感染蚊子的微生物，以及免疫系统的激活如何影响繁殖。 这些目标将通过进行分子和功能实验来实现，这些实验分析了蚊子繁殖和免疫的特定方面。 该研究的更广泛的科学影响将大大提高对蚊子免疫力的理解，并与人类和其他脊椎动物的疾病传播有关。 研究结果还将为所有动物的运作过程提供基本见解。 对社会更广泛的影响包括关于影响人类的蚊子生物学的新信息。这些措施还包括对研究生、研究生和本科生进行科学培训，以及制定供初中和高中使用的教育计划。免疫系统通过保护生物体免受感染来提供健康益处，但也有潜在的成本，因为免疫防御可能会自我破坏或消耗能量。 了解这些权衡以及生物体如何调节与生殖等功能相关的免疫防御是长期存在的基本问题，但很难在生理和分子水平上进行研究。 蚊子为解决这些问题提供了一个强大的研究系统，因为繁殖和感染往往是耦合的。 该应用程序的重点是两种激素，胰岛素肽3（ILP3）和卵巢蜕皮激素（OEH），如何调节埃及伊蚊繁殖过程中的免疫力，并选择其他蚊子物种。 具体目标是：1）表征ILP3在血细胞中激活的信号传导和免疫应答，2）评估ILP3和OEH是否激活脂肪体和肠道中的体液防御，3）确定免疫激活是否增强防御或减少繁殖，以及4）评估繁殖期间的免疫激活是否是保守应答。 目标1和2将通过转录组、信号通路和功能研究来解决。 目标3将通过测量病原体死亡率、蚊子存活率和产卵量来解决。 目标4将通过比较分析来解决。 研究结果将为蚊子的内分泌免疫相互作用和所有动物中发生的过程提供新的见解。 研究和教育将通过研究生，研究生和本科生培训相结合。 将为初中和高中学生开发学习模块。 科学成果将发表在同行评审的期刊上，并在科学会议上发表。

Mosquitoes are extremely important insects because most species blood feed on vertebrates to reproduce. Blood feeding also underlies why some mosquitoes transmit microbes like malaria parasites and Zika virus that can cause severe disease in humans. Hormones are molecules that coordinate functions between different organs, tissues and cells. Prior studies implicate specific hormones in regulating mosquito reproduction and immune defenses against disease-causing microbes, but the molecular mechanisms involved are largely unknown. This project will identify the immune responses that hormones activate in mosquitoes after blood feeding, how these immune responses affect microbes that infect mosquitoes, and how activation of the immune system affects reproduction. These goals will be met by conducting molecular and functional experiments that analyze particular aspects of mosquito reproduction and immunity. The broader scientific impacts of the study will significantly enhance understanding of mosquito immunity with applied relevance to disease transmission in humans and other vertebrates. Results will also provide fundamental insights into processes that operate in all animals. Broader impacts to society include new information about the biology of mosquitoes that affect human populations. They also include scientific training of students at the post-graduate, graduate and undergraduate levels, and development of educational programming for use at the middle and high school level.The immune system provides fitness benefits by defending organisms from infection, yet also has potential costs, because immune defenses can be self-damaging or energetically expensive. Understanding these trade-offs and how organisms regulate immune defenses relative to functions like reproduction are issues of long-standing, fundamental interest, yet are difficult to study at the physiological and molecular level. Mosquitoes provide a powerful study system for addressing these questions because reproduction and infection are often coupled. This application focuses on how two hormones, insulin peptide 3 (ILP3) and ovary ecdysteroidogenic hormone (OEH), regulate immunity during reproduction of Aedes aegypti and select other mosquito species. Specific aims are: 1) characterize the signaling and immune responses ILP3 activates in hemocytes, 2) assess whether ILP3 and OEH activate humoral defenses in the fat body and gut, 3) determine whether immune activation enhances defense or reduces reproduction, and 4) assess whether immune activation during reproduction is a conserved response. Aims 1 and 2 will be addressed through transcriptome, signaling pathway, and functional studies. Aim 3 will be addressed by measuring pathogen mortality, mosquito survival, and egg production. Aim 4 will be addressed through comparative assays. Results will provide new insights into endocrine-immune interactions in mosquitoes and processes that occur in all animals. Research and education will be integrated through post-graduate, graduate and undergraduate training. Study modules will be developed for middle and high school students. Scientific results will be published in peer-reviewed journals and presented at scientific meetings.