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: 10892437
• 负责人: Dana M Hawley
• 金额: $ 11.94万
• 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/10892437
• 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，由先前的病原体暴露产生的免疫保护通常是高度可变的。尽管如此，先前暴露于病原体在诱导宿主易感性的群体水平变化中的作用，以及病原体的选择如何随着时间的推移改变这种异质性，在很大程度上仍然未被探索。此外，宿主的易感性变化的方式出现从病原体性状之间的相互作用，如毒力，和主机特性，如获得性保护，是预测病原体菌株将如何演变和共存的广度主机-病原体系统的关键特征是不完全的保护。虽然理论模型表明宿主异质性对病原体动力学和进化的易感性的关键下游后果，但很少有机会以经验方式参数化这些模型并测试其预测。在这里，我们混合理论和实验在一个易于处理的自然系统-家雀和一种常见的结膜细菌病原体-探索一个未被充分考虑，但广泛相关的机制的异质性易感性：可变的主机保护从以前的病原体暴露。这种先前暴露如何诱导或抑制易感性的群体水平异质性将取决于几个因素，包括1）个体在流行病期间经历的先前病原体暴露的程度，以及因此产生的保护变化，然后通过免疫力减弱而丧失（生态过程）;（2）在较长的时间尺度（进化过程）上，病原体驱动的选择在给定种群中对寄主易感性的程度。宿主易感性中的异源性也是特定于给定病原体的，因此可以受到与宿主先前暴露相互作用的病原体的性状（例如毒力）的影响。我们将评估这些理论及其流行病学和进化的后果-在个别雀与不同的历史，以前的病原体暴露，在不同的历史，病原体驱动的选择种群，和不同的毒力的病原体菌株。这项工作迭代地将经验方法与流行病学和进化模型相结合，以测试：1）先前暴露于病原体如何通过生态和进化过程影响易感性的宿主异质性，2）感染诱导异质性的流行病学后果，以及3）先前暴露如何与病原体性状相互作用以影响异质性，菌株共存和毒力进化。通过这样做，该项目将产生新的和不同的见解，在很大程度上研究不足，但关键形式的主机异质性。