Immunity in an Ecological Context: The Intersection of Host Physiology, Medicinal Food Plants and Microbiomes in a Natural Butterfly-parasite System

生态背景下的免疫：天然蝴蝶寄生虫系统中宿主生理学、药用植物和微生物组的交叉点

• 批准号: 1557724
• 负责人: Jacobus de Roode
• 金额: $ 86.85万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1557724&HistoricalAwards=false
• 关键词: Immunity; Ecological; Context; Intersection; Host

Almost all organisms are attacked by parasites. Recent studies have shown that many animals, from butterflies to chimpanzees, can protect themselves against parasites through self-medication (the use of anti-parasitic substances or diets). However, the mechanisms by which medication behaviors reduce parasite infection and disease remain poorly understood. This project focuses on monarch butterflies and their protozoan parasites. Monarch caterpillars are specialist feeders on milkweed plants, and milkweeds vary in their concentrations and toxicity of chemicals called cardenolides. When feeding on toxic milkweed, monarchs become less sick, and infected female butterflies preferentially lay their eggs on toxic milkweed to reduce disease in their offspring. This project will determine whether toxic milkweeds reduce disease by directly killing parasites, by increasing the immune response of monarchs, or by providing monarchs with a gut flora that prevents parasite infection. Beyond monarch butterflies, this project has broad relevance to other animals, many of which use medicinal plants. The parasites studied here are related to parasites causing disease in agricultural animals and humans, thus elucidating the anti-parasitic activity of milkweed chemicals could have future applications for treating disease. The project will also integrate research with education, by training graduate and undergraduate students, including those from underrepresented groups in science. The researchers will also develop lesson modules with the Wylde Center, an Atlanta-based non-profit organization that teaches environmental awareness through community-garden based outdoor programs. As part of this, the project will directly contribute to the science education of thousands of K-12 students. Hosts have evolved a range of defenses against their parasites, including behavioral and microbial defenses. Such defenses may have important consequences for the evolution of physiological immunity, but research on the interplay between physiological immunity, behavioral immunity and microbial protection remains scarce. This project will study the interaction between monarch butterflies, their milkweed host plants and their protozoan parasites to address three hypotheses: (1) behavioral use of medicinal milkweeds directly decreases parasite infection, rendering physiological immunity superfluous and reducing investment in such immune mechanisms; (2) medicinal milkweeds do not reduce monarch immunity but instead exert their protective effects by enhancing physiological immune responses; and (3) medicinal milkweeds modulate monarch midgut microbiota to a state that confers resistance to parasite infection. These hypotheses will be addressed by elucidating immune responses differentially mounted upon infection of butterflies from resistant and susceptible populations, comparing anti-parasite immune responses in monarchs fed on medicinal and non-medicinal milkweed plants, and by analyzing the effects of milkweed secondary and nutritional chemicals on monarch immunity and resistance. In addition, comparison of the midgut microbiota of monarchs reared on medicinal and non-medicinal milkweeds will be coupled with experiments manipulating gut microbiota to test for the effect of medicinal milkweed microbial communities on monarch resistance to infection. The researchers will use a combination of fieldwork, controlled experiments and next generation sequencing technology, including the use of RNASeq to quantify differential immune responses and MiSeq to quantify bacterial and fungal caterpillar gut communities.

几乎所有的生物都受到寄生虫的攻击。最近的研究表明，从蝴蝶到黑猩猩，许多动物可以通过自我药物（使用抗寄生物或饮食）来保护自己免受寄生虫的影响。但是，药物行为减少寄生虫感染和疾病的机制仍然很少了解。该项目着重于君主蝴蝶及其原生动物寄生虫。君主毛毛虫是乳草植物上的专业喂食器，乳草的浓度和毒性变化了，称为Cardenolides。当以有毒的乳草为食时，君主会减少病人，而感染的雌性蝴蝶优先将卵产在有毒的乳草上，以减少其后代的疾病。该项目将通过直接杀死寄生虫，增加君主的免疫反应或通过为君主提供防止寄生虫感染的肠道菌群来确定有毒的乳草是通过直接杀死寄生虫来减少疾病的。除了君主蝴蝶之外，该项目与其他动物具有广泛的相关性，其中许多动物使用了药用植物。这里研究的寄生虫与引起农业动物和人类疾病的寄生虫有关，因此阐明了乳草化学物质的抗寄生活性，可能会在治疗疾病中有未来的应用。该项目还将通过培训毕业生和本科生，包括科学领域代表性不足的群体的研究，将研究与教育整合。研究人员还将与位于亚特兰大的非营利组织Wylde Center一起开发课程模块，该组织通过基于社区的户外计划来教授环境意识。为此，该项目将直接为数千名K-12学生的科学教育做出贡献。宿主已经进化了针对其寄生虫的一系列防御，包括行为和微生物防御。这种防御可能会对生理免疫的演变产生重要影响，但是对生理免疫，行为免疫和微生物保护之间相互作用的研究仍然很少。该项目将研究君主蝴蝶，其乳草宿主植物和其原生动物寄生虫之间的相互作用，以解决三个假设：（1）药物乳草的行为使用直接降低寄生虫感染，使生理免疫力过多，并减少这种免疫机制的投资； （2）药用乳草不会降低君主免疫，而是通过增强生理免疫反应发挥保护作用； （3）药用乳草将Monarch Midgut Microbiota调节至赋予寄生虫感染的状态。这些假设将通过阐明在耐药和易感人群感染蝴蝶后差异上安装的免疫反应来解决这些假设，从而比较了在药物和非中型乳草植物上喂养的君主的抗寄生虫免疫反应，并分析了乳草二级和营养化学物质对君主免疫力和耐药性的影响。此外，比较在药用和非中等乳草上饲养的君主的中肠菌群，将与操纵肠道微生物群的实验结合，以测试药物乳草微生物群落对君主抵抗感染的影响。研究人员将结合现场工作，受控实验和下一代测序技术，包括使用RNASEQ来量化差异免疫反应和Miseq来量化细菌和真菌毛毛虫肠道群落。