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

在单一宿主内共同发生的寄生虫之间的相互作用对感染结果产生深远影响，从个体宿主内的疾病严重程度和进展到疾病在人群中传播的模式。由于大多数宿主被一种以上的寄生虫感染，并发感染（或合并感染）已成为野生动物、兽医和人类健康面临的主要挑战。因此，对合并感染的研究在包括免疫学、微生物学、疾病生态学和进化、流行病学和公共卫生在内的广泛学科中获得了关注。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）这些相互作用对脆弱宿主感染模式的影响是什么？尽管对共同感染的关注越来越多，但我们对基于实验室的共同感染寄生虫和个体宿主结果之间相互作用机制的见解如何转化为现实世界中的宿主和病原体生态和进化的理解仍然存在根本差距。本提案中概述的研究将通过在自由放养的野生动物系统中调查蠕虫（胃肠道线虫）和牛结核病（牛分枝杆菌，TB）之间的相互作用来帮助弥合这一差距。本提案结合实验、田间、遗传和建模方法，扩展了过去在野生非洲水牛（Syncerus caffer）上的工作，这些工作表明，活跃的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特定目标：(1)确定将蠕虫耐药性与结核病个体结果变化联系起来的免疫机制；(2)量化结核介导的选择对水牛寄生虫抗性的影响；(3)研究选择性去除感染结核病的水牛与蠕虫相关性状对蠕虫种群动态的影响；(4)研究潜伏的、寄生虫相互作用介导的选择对结核毒力的影响。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，以应对合并感染的全球挑战及其对宿主人群疾病结局的影响。该研究对寄生虫如何相互作用以及对宿主和寄生虫生态和进化的影响提出了新的假设，对理解人类、牲畜和野生动物的疾病动态具有重要意义。

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.