Stress hormone effects on disease resistance, tolerance and transmission

应激激素对疾病抵抗力、耐受性和传播的影响

• 批准号: 1257773
• 负责人: Lynn Martin
• 金额: $ 60.41万
• 依托单位: University of South Florida
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1257773&HistoricalAwards=false
• 关键词: Stress; hormone; effects; disease; resistance

Superspreaders are disproportionately responsible for the infections of other hosts. Perhaps the best-known human superspreader was Typhoid Mary, who caused 53 deaths due to Salmonella bacteria transmission. Although the frequency of "Typhoid Marys" is unclear, they are probably not rare. Superspreading is implicated in the rapid expansion of SARS (Sudden Acute Respiratory Syndrome) and HIV across the globe. For most infectious diseases, 20% of hosts cause 80% of infections. The goal of this research is to determine whether glucocorticoids, major vertebrate stress hormones that have been implicated in disease transmission, are involved in superspreading. Stress hormones could impact superspreading by affecting how parasites (or vectors, such as mosquitos and biting flies) choose hosts on which to feed, how hosts resist or tolerate parasites, or how hosts transmit parasites to other hosts or vectors. Surprisingly, there has never been a systematic study of the effects of stress hormones on all aspects of one complex host-vector-parasite system. This knowledge gap is significant and deserves attention because many anthropogenic and natural factors alter stress hormone regulation, and these factors are increasingly important in the context of global change. By knowing how and when stress hormones affect host-parasite interactions, we may become better able to predict and control zoonotic disease outbreaks. Intellectual merit: To investigate the role of stress hormones in superspreading, interactions among zebra finches (ZEFI), Culex pipiens mosquitos, and West Nile virus (WNV) will be studied. WNV was chosen because it has decimated some songbird populations and is thought responsible for more than 33,000 human infections and 1150 deaths. ZEFI and Culex were chosen because their genomes have been sequenced, providing opportunities for strong experimental approaches. Stress hormones are predicted to impact i) ZEFI behavior to Culex exposure, ii) Culex blood-feeding preference on ZEFI, iii) ZEFI resistance to WNV infection, iv) ZEFI tolerance of WNV infection, and/or v) ZEFI competency to transmit WNV to Culex. Ultimately, data will be used to determine directly when stress hormones have the largest impacts, information valuable for human and wildlife populations.Broader impacts: In animals, superspreading appears important for the transmission of several zoonotic diseases (infections that spill from animal into human populations) such as West Nile virus and some hantaviruses. In the context of global change, basic research on understanding superspreading has significant societal value because zoonotic diseases are predicted to become more prevalent. Collaboration with the Tampa Museum of Science and Industry, which attracts more than one million guests annually, will include the development of a Science Works Theater that helps the public understand disease ecology. Training workshops for Hillsborough County high school teachers will also be held, providing teachers tools to train incipient scientists in modern disease biology. For USF students, about 40% of whom come from under-represented backgrounds, robust learning experiences will be provided. Individuals on the project will learn animal husbandry, minor surgeries, how to work in a high-security infectious disease research facility, modern lab assays, data analysis, and scientific writing.

超级传播者对其他宿主的感染负有不成比例的责任。也许最著名的人类超级传播者是伤寒玛丽，它因沙门氏菌传播导致53人死亡。尽管“玛丽台风”的发生频率尚不清楚，但它们可能并不罕见。超级传播与SARS(突发急性呼吸综合征)和艾滋病毒在全球范围内的迅速扩张有关。对于大多数传染病来说，20%的宿主导致了80%的感染。这项研究的目标是确定糖皮质激素是否参与了超级传播。糖皮质激素是脊椎动物的主要应激激素，与疾病传播有关。应激激素可能通过影响寄生虫(或媒介，如蚊子和叮咬的苍蝇)选择寄主的方式，宿主如何抵抗或容忍寄生虫，或者宿主如何将寄生虫传播给其他宿主或媒介，来影响超级传播。令人惊讶的是，从来没有系统地研究应激激素对一个复杂的宿主-病媒-寄生虫系统的各个方面的影响。这一认识差距是显著的，值得注意，因为许多人为和自然因素改变了应激激素调节，而这些因素在全球变化的背景下变得越来越重要。通过了解应激激素如何以及何时影响宿主和寄生虫的相互作用，我们可能会变得更好地预测和控制人畜共患疾病的爆发。智力优势：为了研究应激激素在超级传播中的作用，我们将研究斑马雀(Zefi)、库蚊和西尼罗河病毒(WNV)之间的相互作用。之所以选择西尼罗河病毒，是因为它杀死了一些鸣禽种群，被认为是导致超过3.3万人感染和1150人死亡的罪魁祸首。之所以选择Zefi和Culex，是因为它们的基因组已经测序，为强有力的实验方法提供了机会。应激激素被预测影响1)对库蚊暴露的Zefi行为，ii)对Zefi的取血偏好，III)Zefi对西尼罗河病毒感染的抵抗力，iv)Zefi对WNV感染的耐受性，和/或v)Zefi将WNV传播给库蚊的能力。最终，数据将被用来直接确定压力荷尔蒙何时产生最大影响，这是对人类和野生动物种群有价值的信息。广泛的影响：在动物中，超级传播似乎对几种人畜共患病(从动物传播到人类种群的感染)的传播很重要，如西尼罗河病毒和一些汉坦病毒。在全球变化的背景下，了解超级传播的基础研究具有重大的社会价值，因为人畜共患疾病预计将变得更加普遍。与每年吸引100多万名游客的坦帕科学和工业博物馆的合作，将包括开发一个科学作品剧院，帮助公众了解疾病生态。还将为希尔斯伯勒县高中教师举办培训讲习班，为教师提供工具，培训现代疾病生物学方面的初学者。对于USF的学生，其中约40%来自代表性不足的背景，将提供强大的学习体验。该项目的个人将学习畜牧业、小手术、如何在高度安全的传染病研究机构工作、现代实验室分析、数据分析和科学写作。