Ecophysiology of a host-parasite interaction that causes metabolic disease

导致代谢疾病的宿主-寄生虫相互作用的生态生理学

• 批准号: 1457237
• 负责人: Rudolf Schilder
• 金额: $ 41万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1457237&HistoricalAwards=false
• 关键词: Ecophysiology; host; parasite; interaction; causes

The causes and rates at which humans and other mammals develop metabolic diseases such as diabetes and obesity are complex. Biomedical research has traditionally focused on how shifts in diet and physical activity affect metabolism in mammalian model organisms such as rats and mice. While these two factors are known to be significant, there is very little information on other conditions that can cause or contribute to metabolic disease. The range of animal species that can develop metabolic disease is also unknown. The investigators recently demonstrated that diabetes and obesity are not unique to mammals and occur in natural populations of dragonflies as a consequence of gut infection by a protozoan parasite. Preliminary data indicate that the level of acidity in water bodies that dragonflies inhabit is a strong predictor of rates of infection and therefore, metabolic disease in the dragonfly species. The role of infection in the development of metabolic disease is poorly understood in any animal system. This project represents a unique opportunity to provide new ecological and physiological insights and will allow in-depth studies on this problem. This integrative project will experimentally link natural variation in water acidity, dragonfly gut microbiome composition and parasitic infection susceptibility to dragonfly metabolic and other performance phenotypes. This work will underline the importance of environmental factors to metabolic disease. This project also has broad relevance given the growing prevalence of natural insect-protozoan parasite interactions that cause disease in humans (e.g. malaria, toxoplasmosis) and in species of economic importance (e.g. honey bees, bumblebees) to humans. The causative role of infection in the development of metabolic disease such as obesity is poorly understood in any animal system. The project proposes to conduct experiments that will extend previous work on this dragonfly host-parasite interaction and provide novel insights into the ecophysiology of infection-related metabolic disease in an insect. Based on new ecological and physiological data from this system, these studies will examine the hypotheses that both environmental pH and chemical interactions of parasite and gut microbiota are important drivers of susceptibility to infection, and its escalation into metabolic disease and reduced fitness in the dragonfly host. The investigator will 1) use full factorial treatment designs to examine effects of environmental (water) pH and exposure to infectious spores on larval and host gut microbiome composition and parasite load, 2) determine infection effects on flight muscle performance and fuel use during high intensity flight behavior (field high speed videography, in situ work loop and respiratory quotient assays), and 3) assess the extent of host manipulation by the parasite through examination of systemic immunity in healthy and infected adults, in response to parasite excretory/secretory products and to heat-inactivated bacterial cultures.

人类和其他哺乳动物发生代谢性疾病（如糖尿病和肥胖症）的原因和速度很复杂。生物医学研究传统上集中在饮食和体力活动的变化如何影响哺乳动物模型生物体（如大鼠和小鼠）的代谢。虽然已知这两个因素是重要的，但关于可能导致或导致代谢疾病的其他条件的信息很少。也不知道有哪些动物会患上代谢性疾病。研究人员最近证明，糖尿病和肥胖症并不是哺乳动物所独有的，而是由于原生动物寄生虫的肠道感染而发生在自然种群的蜻蜓中。初步数据表明，蜻蜓栖息的水体的酸度水平是感染率的一个强有力的预测因素，因此，蜻蜓物种的代谢疾病。在任何动物系统中，对感染在代谢性疾病发展中的作用都知之甚少。该项目代表了一个独特的机会，提供新的生态和生理见解，并将允许对这个问题进行深入研究。这个综合项目将通过实验将水酸度的自然变化，肠道微生物组组成和寄生虫感染易感性与代谢和其他性能表型联系起来。这项工作将强调环境因素对代谢疾病的重要性。鉴于自然界昆虫-原生动物寄生虫相互作用日益普遍，导致人类疾病（如疟疾、弓形虫病）和对人类具有经济重要性的物种（如蜜蜂、大黄蜂），该项目也具有广泛的相关性。在任何动物系统中，对感染在代谢性疾病（如肥胖症）发展中的致病作用了解甚少。该项目建议进行实验，将扩展以前的工作，这种寄生虫-寄生虫相互作用，并提供新的见解感染相关的代谢疾病在昆虫的生态生理学。基于来自该系统的新的生态和生理数据，这些研究将研究以下假设：环境pH值和寄生虫与肠道微生物群的化学相互作用是感染易感性的重要驱动因素，以及其升级为代谢疾病和降低宿主的适应性。研究人员将1）使用全因子处理设计来检查环境（水）pH值和暴露于感染性孢子对幼虫和宿主肠道微生物组组成和寄生虫负荷的影响，2）确定感染对高强度飞行行为期间飞行肌肉性能和燃料使用的影响（现场高速摄像、原位工作环和呼吸商测定），和3）通过检查健康和感染成人的全身免疫来评估寄生虫操纵宿主的程度，响应寄生虫排泄/分泌产物和热灭活细菌培养物。