Influence of gut microbiota on vector competence of disease transmitting insects

肠道微生物群对传播疾病的昆虫媒介能力的影响

• 批准号: 9924459
• 负责人: Jingwen Wang
• 金额: $ 14.18万
• 依托单位: FUDAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-12 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9924459
• 关键词: African; African Trypanosomiasis; Anopheles Genus; Antiparasitic Agents; Bacteria; Biology; Communicable Diseases; Competence; Culicidae; Disease; Disease Vectors; Drug resistance; Goals; Human; Immune; Immune response; Immune signaling; Immunity; Infection; Influentials; Innate Immune Response; Innate Immune System; Insect Vectors; Insecta; Insecticide Resistance; Insecticides; Interruption; Knowledge; Light; Malaria; Metabolic; Metabolism; Methods; Microbe; Natural Resistance; Nutrient; Parasite resistance; Parasites; Parasitic infection; Pattern recognition receptor; Phase; Phenotype; Plasmodium; Play; Population; Predisposition; Protein Family; Recording of previous events; Regulation; Role; Shapes; Signal Pathway; Signal Transduction; Structure; Structure-Activity Relationship; Symbiosis; System; Trypanosoma; Tsetse Flies; Vaccines; Vector-transmitted infectious disease; Wigglesworthia; amidase; antimicrobial; antimicrobial peptide; burden of illness; comparative; density; disease transmission; fitness; gut microbiota; host microbiota; life history; member; metabolomics; microbiome; microbiota; novel; nutrient metabolism; pathogen; peptidoglycan recognition protein; prevent; protein function; receptor; reproductive; symbiont; tool; trait; transmission process; vector; vector competence; vector control; vector mosquito; vector-borne

Diseases transmitted by insects (vector borne) account for over 17% of the infectious disease burden globally. Most of these diseases lack efficient mammalian vaccines or treatments, and thus heavily rely on vector control to prevent or reduce transmission. Anopheles and tsetse fly are the two vectors involved in malaria and sleeping sickness transmission, respectively. Current vector control methods largely involve the use of insecticides that are environmentally undesirable, and have diminishing efficacy in light of the emergence of insecticide resistance observed in insects. Understanding the mechanisms that influence vector-parasite transmission biology can help develop new control methods. There is growing evidence that the capacity to transmit parasites (vector competence) is influenced by vector innate immune responses and associations with native microbes. The two disease vectors, mosquitoes and tsetse flies, have varying life histories and different associations with gut microbiota. An important component of the innate immune response to pathogens involves Peptidoglycan Recognition Proteins, PGRPs, which recognize pathogen specific molecules and regulate host immune responses that ultimately clear pathogens. We have identified that the PGRP repertoire and functions in tsetse and mosquito vary in accordance with their different life histories and symbiotic associations. We also found that native microbiota influence vector competence through essential roles they play in host immunity and metabolism. This proposal builds on our preliminary studies and expands our previous findings to: 1) characterize and compare PGRP functions that differ in Anopheles and tsetse focusing on PGRP-LB and PGRP-LD and 2) investigate immune and metabolic contribution of the gut microbiota to vector competence. Implementation of our goals will expand our knowledge on 1) the structure and regulation of PGRPs contributing to vector competence, and 2) influence of metabolic interactions between vectors and microbiota on disease transmission traits. These findings have the potential to advance knowledge on tripartite interactions between vectors, symbionts and parasites, and to develop novel targets for disrupting pathogen transmission.

昆虫传播的疾病（病媒传播）占全球传染病负担的17%以上。这些疾病大多缺乏有效的哺乳动物疫苗或治疗方法，因此严重依赖病媒控制来预防或减少传播。按蚊和采采蝇分别是传播疟疾和昏睡病的两种媒介。目前的病媒控制方法主要涉及使用对环境不利的杀虫剂，并且鉴于在昆虫中观察到的杀虫剂抗药性的出现，杀虫剂的效力逐渐降低。了解影响媒介-寄生虫传播生物学的机制有助于开发新的控制方法。越来越多的证据表明，传播寄生虫的能力（载体能力）受到载体先天免疫反应和与天然微生物的关联的影响。蚊子和采采蝇这两种病媒有着不同的生活史，与肠道微生物群有着不同的联系。对病原体的先天免疫应答的一个重要组成部分涉及肽聚糖识别蛋白（PGRP），其识别病原体特异性分子并调节最终清除病原体的宿主免疫应答。我们已经确定，采采蝇和蚊子的PGRP库和功能根据其不同的生活史和共生协会而变化。我们还发现，天然微生物群通过它们在宿主免疫和代谢中发挥的重要作用影响载体能力。该提议建立在我们的初步研究基础上，并将我们先前的发现扩展到：1）表征和比较在按蚊和采采蝇中不同的PGRP功能，重点是PGRP-LB和PGRP-LD，以及2）研究肠道微生物群对载体能力的免疫和代谢贡献。我们目标的实现将扩大我们对以下方面的知识：1）有助于载体能力的PGRP的结构和调控，以及2）载体和微生物群之间的代谢相互作用对疾病传播特征的影响。这些发现有可能促进对媒介、共生体和寄生虫之间三方相互作用的认识，并开发新的靶点来破坏病原体的传播。