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.

几乎所有生物体都会受到寄生虫的攻击。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疗（使用抗寄生虫物质或饮食）来保护自己免受寄生虫侵害。然而，药物行为减少寄生虫感染和疾病的机制仍知之甚少。该项目的重点是帝王蝶及其原生动物寄生虫。帝王毛虫是马利筋植物的专门捕食者，而马利筋的化学物质卡烯内酯的浓度和毒性各不相同。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。该项目将确定有毒马利筋是否通过直接杀死寄生虫、增加帝王蝶的免疫反应或为帝王蝶提供预防寄生虫感染的肠道菌群来减少疾病。除了帝王蝶之外，该项目与其他动物也有广泛的相关性，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，因此阐明马利筋化学物质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 Center 合作开发课程模块，Wylde Center 是一家位于亚特兰大的非营利组织，通过基于社区花园的户外项目教授环境意识。作为该项目的一部分，该项目将直接为数千名 K-12 学生的科学教育做出贡献。宿主已经进化出一系列针对寄生虫的防御措施，包括行为和微生物防御。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。该项目将研究帝王蝶、其马利筋寄主植物和原生动物寄生虫之间的相互作用，以解决三个假设：（1）药用马利筋的行为使用直接减少寄生虫感染，使生理免疫变得多余，并减少对此类免疫机制的投资； (2)药用马利筋不会降低帝王蝶的免疫力，而是通过增强生理免疫反应发挥保护作用； (3)药用马利筋将帝王蝶中肠微生物群调节至抵抗寄生虫感染的状态。这些假设将通过阐明抗性和易感群体的蝴蝶感染时不同的免疫反应、比较以药用和非药用马利筋植物为食的帝王蝶的抗寄生虫免疫反应，以及分析马利筋次生和营养化学物质对帝王蝶免疫和抵抗力的影响来解决。此外，比较药用和非药用马利筋养殖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性的影响。研究人员将结合实地考察、对照实验和下一代测序技术，包括使用 RNASeq 来量化差异免疫反应，以及使用 MiSeq 来量化细菌和真菌毛毛虫肠道群落。