Resistance versus tolerance: an evolutionary physiology approach

抵抗与耐受：进化生理学方法

• 批准号: 352425757
• 负责人: Dr. Sophie Armitage
• 金额: --
• 依托单位: Institut für Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/352425757?language=en
• 关键词: Resistance; versus; tolerance; evolutionary; physiology

A host can defend itself against an infection by directly reducing pathogen numbers, i.e., host resistance, or by reducing the harm that the infection does to its fitness, i.e., host tolerance. Given that resisting an infection can be costly for the host and result in autoimmune damage, it follows that a more resistant host is not necessarily fitter than a less resistant host. Tolerance is therefore an essential concept because it describes how well hosts are able to reduce the fitness costs of a given pathogen load. Resistance and tolerance are predicted to have contrasting effects on host-pathogen evolution and the spread of infectious diseases. It is therefore important to understand infection in the context of these two concepts, and we here propose to study them using an insect host, Drosophila melanogaster, and bacterial pathogens. Bacterial infections are dynamic processes. This means that host responses to pathogen replication and damage, and pathogen replication and counter-responses to the host, will change over time. In addition, it is becoming increasingly clear that bacterial infections can persist for the lifetime of an insect. This can be up to weeks or months in D. melanogaster, potentially increasing the opportunity and window for pathogen evolution. Both the dynamics and persistence of infection lead to the question of when during the infection, the host response, i.e., resistance or tolerance, should be captured, and how this affects our interpretation of host defences. In this project we propose to examine resistance and tolerance in the light of the dynamics and persistence of infection, through four complimentary objectives. We propose 1. To simultaneously examine the proteomic responses of hosts to persistent infections and the metabolic state of the persisting bacteria; 2. To identify where the bacteria are persisting inside their hosts; 3. To investigate the dynamics of fecundity tolerance in persistent infections, and the trade-off between fecundity- and mortality-tolerance, and 4. To examine what effects high and low resistance and fecundity tolerance have on host protein expression during persistent infections. The results from this project will provide novel insights into bacterial persistence, the host and pathogen responses during persistent infections, and resistance and tolerance along the trajectory of the infection process.

宿主可以通过直接减少病原体数量来保护自身免受感染，即，宿主抗性，或通过减少感染对其适应性的损害，即，寄主耐受性鉴于抵抗感染对宿主来说可能是昂贵的，并导致自身免疫性损伤，因此抗性更强的宿主不一定比抗性较低的宿主更健康。因此，耐受性是一个重要的概念，因为它描述了宿主如何能够降低给定病原体负荷的适应性成本。预计抗性和耐受性对宿主-病原体进化和传染病传播具有截然不同的影响。因此，在这两个概念的背景下理解感染是很重要的，我们在这里建议使用昆虫宿主果蝇和细菌病原体来研究它们。细菌感染是一个动态过程。这意味着宿主对病原体复制和破坏的反应，以及病原体复制和对宿主的反反应，将随着时间的推移而改变。此外，越来越清楚的是，细菌感染可以持续昆虫的一生。在D中，这可能长达数周或数月。黑腹菌，潜在地增加了病原体进化的机会和窗口。感染的动力学和持续性都导致了一个问题，即在感染期间，宿主的反应，即，抗性或耐受性，以及这如何影响我们对宿主防御的解释。在这个项目中，我们建议通过四个互补的目标，根据感染的动态和持续性来检查抗性和耐受性。我们建议1.同时检测宿主对持续感染的蛋白质组反应和持续感染细菌的代谢状态; 2.确定细菌在宿主体内的位置; 3.探讨持续感染时生殖力耐受的动态变化，以及生殖力耐受和死亡耐受之间的权衡。研究高、低抗性和繁殖力耐受对持续感染过程中宿主蛋白表达的影响。该项目的结果将为细菌持久性，持续感染期间的宿主和病原体反应以及感染过程沿着的抗性和耐受性提供新的见解。