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，先前接触病原体所产生的免疫保护往往是高度可变的。然而，先前暴露于病原体在诱导宿主易感性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，在很大程度上仍未被探索。此外，宿主的易感性变化来自病原体性状（如毒力）和宿主性状（如获得性保护）之间的相互作用，这是预测病原体菌株如何在以不完全保护为特征的宿主-病原体系统的广度中进化和共存的关键。虽然理论模型表明宿主异质性对病原体动力学和进化易感性的关键下游影响，但很少有机会对这些模型进行经验参数化并测试其预测。在这里，我们将理论和实验结合在一个可处理的自然系统中——家雀和一种常见的结膜细菌病原体——来探索一个未被充分考虑但广泛相关的易感性异质性机制：先前病原体暴露产生的可变宿主保护。这种先前接触如何诱发或抑制群体水平易感性的异质性将取决于几个因素，包括1)流行期间个人先前接触病原体的程度，以及由此产生的保护的差异，然后因免疫力下降而丧失（生态过程）；2)在更长时间尺度（进化过程）中，特定种群中病原体驱动的选择对宿主易感性的影响程度。宿主易感性的异质性也是特定于特定病原体的，因此可能受到与宿主先前暴露相互作用的病原体特征（例如毒力）的影响。我们将评估这些理论——以及它们的流行病学和进化结果——在具有不同先前病原体暴露历史的单个雀中，在具有不同病原体驱动选择历史的种群中，以及在具有不同毒力的病原体菌株中。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宿主易感性的异质性，2)暴露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特征相互作用以影响异质性，菌株共存和毒力进化。通过这样做，该项目将对宿主异质性的主要形式产生新的和不同的见解。