Endocrine regulation of immunity and reproduction in mosquitoes

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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.