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: 10247051
• 负责人: Vanessa Ezenwa
• 金额: $ 34.25万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247051
• 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.

单个宿主中同时存在的寄生虫之间的相互作用对从疾病严重程度和单个宿主的进展到疾病模式到跨种群的疾病模式，对感染结果产生了深远的影响。由于大多数宿主都被多种类型的寄生虫感染，因此同时感染（或共同感染）已成为野生动植物，兽医和人类健康的关键挑战。结果，对共同感染的研究在广泛的学科中获得了关注，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相同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？ （ii）这些相互作用对弱势宿主感染模式的后果是什么？尽管人们对共同感染的关注越来越高，但我们对基于实验室的见解如何对共同感染的寄生虫与单个宿主的结果之间的基础机制的见解的理解仍然存在。该提案中概述的研究将通过调查蠕虫（胃肠道线虫）和牛结核病（Bovis，TB，TB）之间的相互作用来帮助弥合这一差距。该提案结合了实验，田间，遗传和建模方法的结合，扩展了野生非洲水牛（calencerus caffer）的过去工作，这表明活跃的线虫感染和对线虫对线虫的适应性都可以作为TB疾病疾病的有效驱动因素，以解决四个相互链接的特定特定目标：1（1）链接机制：1（1）（1）（1）（1）（1）（1）（1）（1）（1）链接的链接。结核病的结果； （2）量化在布法罗中蠕虫抗性的TB介导的选择的强度； （3）研究与蠕虫相关的特征的选择性去除TB感染的水牛如何影响蠕虫人口动力学； （4）检查对结核病毒力的隐性，寄生虫相互作用介导的选择的潜力。该项目将生态学，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整合在一起，以应对共同感染的全球挑战及其对宿主人群中疾病结果的影响。该研究提出了关于寄生虫如何相互作用的新假设，以及对宿主和寄生虫生态学和进化的后果，对了解人类，牲畜和野生动植物的疾病动态具有重要意义。

项目成果

Immune stability predicts tuberculosis infection risk in a wild mammal.

免疫稳定性可预测野生哺乳动物感染结核病的风险。

• DOI: 10.1098/rspb.2019.1401
• 发表时间: 2019
• 期刊: Proceedings. Biological sciences
• 作者: Seguel,Mauricio;Beechler,BriannaR;Coon,CourtneyC;Snyder,PaulW;Spaan,JohannieM;Jolles,AnnaE;Ezenwa,VanessaO
• 通讯作者: Ezenwa,VanessaO

Characterising interactions between co-infecting parasites using age-intensity profiles.

使用年龄强度分布来表征共同感染寄生虫之间的相互作用。

• DOI: 10.1016/j.ijpara.2019.11.001
• 发表时间: 2020
• 期刊: International journal for parasitology
• 影响因子: 4
• 作者: Park,AndrewW;Ezenwa,VanessaO
• 通讯作者: Ezenwa,VanessaO

Natural resistance to worms exacerbates bovine tuberculosis severity independently of worm coinfection.

对蠕虫的天然抵抗力会加剧牛结核病的严重程度，与蠕虫合并感染无关。

• DOI: 10.1073/pnas.2015080118
• 发表时间: 2021
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Ezenwa,VanessaO;Budischak,SarahA;Buss,Peter;Seguel,Mauricio;Luikart,Gordon;Jolles,AnnaE;Sakamoto,Kaori
• 通讯作者: Sakamoto,Kaori