Ecological and evolutionary causes and consequences of host heterogeneity induced by prior exposure

先前暴露引起的宿主异质性的生态和进化原因和后果

• 批准号: 10379532
• 负责人: Dana M Hawley
• 金额: $ 43.46万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-02 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10379532
• 关键词: Disease Outbreaks; Epidemic; Epidemiology; Evolution; Exposure to; Finches; Heterogeneity; Human; Immune; Immunity; Individual; Modeling; Population; Predisposition; Process; Recording of previous events; Role; System; Testing; Theoretical model; Time; Vaccination; Variant; Virulence; Work; experience; experimental study; insight; novel; pathogen; pathogen exposure; pathogenic bacteria; theories; trait

There is growing recognition that the immune protection generated by prior pathogen exposure is often highly variable. Nonetheless, the role of prior exposure to pathogens in inducing population-level variation in host susceptibility, and how selection from pathogens alters such heterogeneity over time, remains largely unexplored. Further, the way in which host variation in susceptibility emerges from interactions between pathogens traits, such as virulence, and host traits, such as acquired protection, is key for predicting how pathogen strains will evolve and coexist in the breadth of host-pathogen systems characterized by incomplete protection. While theoretical models suggest key downstream consequences of host heterogeneity in susceptibility for pathogen dynamics and evolution, there have been few opportunities to empirically parameterize such models and test their predictions. Here we blend theory and experiments in a tractable natural system -- house finches and a common conjunctival bacterial pathogen -- to explore an under-considered but broadly relevant mechanism of heterogeneity in susceptibility: variable host protection generated from prior pathogen exposure. How such prior exposure induces or dampens population-level heterogeneity in susceptibility will depend on several factors, including 1) the extent of prior pathogen exposure that individuals experience during epidemics, and thus the variation in protection generated and then lost via waning immunity (ecological processes); and 2) the extent of pathogen-driven selection on host susceptibility in a given population over longer time scales (evolutionary processes). Heterogeneity in host susceptibility is also specific to a given pathogen, and thus can be influenced by traits of pathogens (e.g. virulence) that interact with host prior exposure. We will assess these theories-- and their epidemiological and evolutionary consequences-- among individual finches with varying histories of prior pathogen exposure, across populations with varying histories of pathogen-driven selection, and among pathogen strains that vary in virulence. The work iteratively merges empirical approaches with epidemiological and evolutionary models to test: 1) how prior exposure to pathogens, via both ecological and evolutionary processes, influences host heterogeneity in susceptibility, 2) the epidemiological consequences of exposure-induced heterogeneity, and, 3) how prior exposure interacts with pathogen traits to influence heterogeneity, strain coexistence, and virulence evolution. By doing so, the project will generate novel and diverse insights regarding a largely understudied but key form of host heterogeneity.

越来越多的人认识到，以前接触病原体所产生的免疫保护往往是高度可变的。然而，以前接触病原体在引起寄主易感性的种群水平变异中的作用，以及从病原体中选择如何随着时间的推移改变这种异质性，在很大程度上仍未被探索。此外，病原菌特性(如毒力)和寄主特性(如获得性保护)之间的相互作用产生的寄主敏感性变异是预测病原菌菌株将如何进化并在以不完全保护为特征的广泛的寄主-病原体系统中共存的关键。虽然理论模型表明寄主异质性在病原体动态和进化易感性方面的关键下游后果，但很少有机会对此类模型进行经验参数化并测试其预测。在这里，我们在一个易驯化的自然系统--家雀和一种常见的结膜细菌病原体--中结合理论和实验，以探索一种未被充分考虑但广泛相关的易感性异质性机制：由先前的病原体暴露产生的可变宿主保护。这种先前接触如何诱导或抑制群体水平的易感性异质性将取决于几个因素，包括1)个人在流行期间经历的先前病原体暴露的程度，从而通过免疫力减弱而产生并随后失去的保护的变化(生态过程)；以及2)在较长时间尺度上(进化过程)对给定群体的宿主易感性进行病原体驱动的选择的程度。寄主敏感性的异质性也是特定病原体所特有的，因此可以受到病原体的特性(如毒力)的影响，这些特性与先前接触的寄主相互作用。我们将评估这些理论--以及它们的流行病学和进化结果--在有不同先前病原体暴露史的个体雀中，在有不同病原体驱动选择历史的种群中，以及在毒力不同的病原体菌株之间。这项工作反复地将经验方法与流行病学和进化模型结合起来，以测试：1)先前接触病原体如何通过生态和进化过程影响宿主易感性的异质性，2)暴露诱导的异质性的流行病学后果，以及3)先前暴露与病原体特征如何相互作用影响异质性、菌株共存和毒力进化。通过这样做，该项目将产生关于宿主异质性的一种基本未被研究但关键形式的新颖和多样化的见解。