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，许多动物，从蝴蝶到黑猩猩，可以通过自我药物（使用抗寄生虫物质或饮食）来保护自己免受寄生虫的侵害。然而，药物行为减少寄生虫感染和疾病的机制仍然知之甚少。这个项目的重点是帝王蝶和它们的原生寄生虫。帝王毛虫是乳草植物的专家，乳草在它们的浓度和称为强心内酯的化学物质的毒性方面各不相同。当以有毒的马利筋为食时，帝王蝶的病情会减轻，受感染的雌性蝴蝶会优先在有毒的马利筋上产卵，以减少后代的疾病。该项目将确定有毒乳草是否通过直接杀死寄生虫，通过增加帝王蝶的免疫反应或通过为帝王蝶提供防止寄生虫感染的肠道植物群来减少疾病。除了帝王蝶，这个项目与其他动物有着广泛的相关性，其中许多动物使用药用植物。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，因此阐明了马利筋化学品的抗寄生虫活性可能在未来用于治疗疾病。该项目还将通过培训研究生和本科生，包括那些来自科学领域代表性不足的群体的学生，将研究与教育结合起来。研究人员还将与Wylde中心一起开发课程模块，Wylde中心是一个位于亚特兰大的非营利组织，通过社区花园的户外项目教授环境意识。作为其中的一部分，该项目将直接有助于数千名K-12学生的科学教育。果蝇已经进化出一系列对抗寄生虫的防御措施，包括行为防御和微生物防御。这种防御可能对生理免疫的进化产生重要影响，但对生理免疫，行为免疫和微生物保护之间相互作用的研究仍然很少。本计画将研究黑脉金斑蝶、马利筋寄主植物与原生动物寄生虫之间的互动关系，以验证三个假设：（1）行为上使用药用马利筋直接减少寄生虫感染，使生理免疫变得多余，并减少对这种免疫机制的投资;（2）药用乳草不会降低帝王蝶免疫力，而是通过增强生理免疫反应发挥其保护作用;和（3）药用乳草调节帝王蝶中肠微生物群至赋予对寄生虫感染的抗性的状态。这些假设将通过阐明免疫反应差异安装在感染的蝴蝶从抗性和易感人群，比较抗寄生虫的免疫反应，在君主喂养的药用和非药用马利筋植物，并通过分析马利筋次生和营养化学物质对君主的免疫力和抗性的影响。此外，比较药用和非药用马利筋上饲养的帝王蝶的中肠微生物群将与操纵肠道微生物群的实验相结合，以测试药用马利筋微生物群落对帝王蝶抗感染的影响。研究人员将结合实地调查、对照实验和下一代测序技术，包括使用RNASeq量化差异免疫反应，使用MiSeq量化细菌和真菌毛虫肠道群落。