Coupled Macroparasite-Microparasite Interactions: Ecological and Evolutionary Consequences of Coinfection

大型寄生虫与微型寄生虫的耦合相互作用：共同感染的生态和进化后果

• 批准号: 9794754
• 负责人: Vanessa Ezenwa
• 金额: $ 56.42万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-27 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9794754
• 关键词: Address; African; Animals; Attention; Biology; Bovine Tuberculosis; Buffaloes; Coupled; Discipline; Disease; Disease Outcome; Disease Progression; Ecology; Epidemiology; Evolution; Excision; Genetic Models; Genomics; Health; Helminths; Human; Immune; Immunologics; Immunology; Individual; Infection; Laboratories; Link; Livestock; Mathematical Biology; Mediating; Microbiology; Mycobacterium bovis; Nematoda; Nematode infections; Outcome; Parasites; Pattern; Population; Population Dynamics; Public Health; Research; Resistance; Severities; Severity of illness; Shapes; Syncerus; System; Traction; Translating; Variant; Virulence; Work; base; co-infection; gastrointestinal; insight; novel; pathogen; theories; trait

Interactions between parasites co-occurring within a single host have profound effects on infection outcomes ranging from disease severity and progression within individual hosts to patterns of disease spread across populations. Since most hosts are infected by more than one type of parasite, concurrent infection (or co-infection) has emerged as a key challenge for wildlife, veterinary, and human health. As a consequence, the study of co-infection has gained traction across a wide range of disciplines, including immunology, microbiology, disease ecology and evolution, epidemiology, and public health. Importantly, research in all of these spheres is largely focused on different aspects of the same core questions: (i) what are the causes of interactions between parasites? and (ii) what are the consequences of these interactions for patterns of infection in vulnerable hosts? Despite this increased attention to co-infection, a fundamental gap remains in our understanding of how laboratory-based insights on the mechanisms underlying interactions between co-infecting parasites and the outcomes for individual hosts translate into host and pathogen ecology and evolution in the real world. The research outlined in this proposal will help bridge this gap by investigating interactions between helminths (gastrointestinal nematodes) and bovine tuberculosis (Mycobacterium bovis, TB) in a free-ranging wildlife system. This proposal uses a combination of experimental, field, genetic, and modeling approaches to extend past work in wild African buffalo (Syncerus caffer), which has revealed that both active nematode infection and host adaptation to nematodes serve as potent drivers of variation in TB disease outcomes, to address four inter-related specific aims: (1) Identify the immunological mechanisms linking helminth resistance to variable individual outcomes of TB; (2) Quantify the strength of TB-mediated selection on helminth resistance in buffalo; (3) Investigate how selective removal of TB-infected buffalo with respect to helminth-related traits influences helminth population dynamics; (4) Examine the potential for cryptic, parasite interaction-mediated selection on TB virulence. The project integrates ideas and approaches from ecology, evolutionary biology, immunology, microbiology, genomics, and mathematical biology to address the global challenge of co-infection and its impacts on disease outcomes in host populations. The research poses novel hypotheses about how parasites interact, and the consequences for host and parasite ecology and evolution, with significant implications for understanding disease dynamics in humans, livestock, and wildlife.

寄生虫之间的相互作用共同发生在一个单一的主机有深远的影响感染的结果，从疾病的严重程度和进展，在个别主机的模式，疾病在人群中传播。由于大多数宿主被一种以上类型的寄生虫感染，并发感染（或共感染）已成为野生动物，兽医和人类健康的关键挑战。因此，对合并感染的研究在广泛的学科中获得了牵引力，包括免疫学，微生物学，疾病生态学和进化，流行病学和公共卫生。重要的是，所有这些领域的研究主要集中在同一核心问题的不同方面：（i）寄生虫之间相互作用的原因是什么？以及（ii）这些相互作用对脆弱宿主的感染模式有何影响？尽管对共感染的关注增加，但我们对共感染寄生虫之间相互作用的机制以及个体宿主的结果如何转化为真实的世界中的宿主和病原体生态学和进化的理解仍然存在根本性的差距。本提案中概述的研究将通过调查自由放养的野生动物系统中蠕虫（胃肠道线虫）和牛结核病（牛分枝杆菌，TB）之间的相互作用，帮助弥合这一差距。该建议采用实验、田间、遗传和建模方法相结合的方法，以扩展过去在野生非洲布法罗中的工作（Syncerus caffer），该研究揭示了活动性线虫感染和宿主对线虫的适应都是结核病结果变化的有力驱动因素，以解决四个相互关联的具体目标：（1）确定将蠕虫抗性与TB的可变个体结果联系起来的免疫学机制;（2）量化TB介导的选择对布法罗蠕虫抗性的强度;（3）调查如何选择性地清除结核病感染的布法罗蠕虫相关性状影响蠕虫种群动态;（4）检查潜在的隐蔽，寄生虫相互作用介导的选择结核病毒力。该项目整合了生态学，进化生物学，免疫学，微生物学，基因组学和数学生物学的思想和方法，以应对共同感染及其对宿主人群疾病结果的影响的全球挑战。这项研究提出了关于寄生虫如何相互作用的新假设，以及宿主和寄生虫生态学和进化的后果，对理解人类，牲畜和野生动物的疾病动态具有重要意义。