Host immune suppression as a key adaptation enabling bacterial symbioses

细菌共生体在动植物中广泛存在，常常提供有益的功能，对宿主的生物学产生深远的影响。尤其是昆虫，为了新陈代谢、营养和保护，多次与微生物形成共生环境。昆虫免疫系统的任务是控制和调节有益微生物，同时对抗往往密切相关的病原微生物。一个关键的悬而未决的问题是，昆虫免疫系统是否是不同寄主物种中共生体和病原体的关键媒介。该项目将把尖端基因组学与实验操作相结合，将免疫反应与不同寄主物种之间的共生体联系起来。从机制上了解免疫系统如何与共生体相互作用不仅对了解宿主相关微生物的进化至关重要，而且与传播农作物、牲畜和人类毁灭性疾病的无脊椎动物害虫有关。此外，还为本科生提供了培养下一代STEM研究人员的研究机会。该项目将以蚜虫为模型系统，涉及田纳西诺克斯维尔大学和伦敦玛丽女王大学的研究。蚜虫特别适合这项工作，因为它们与微生物共生体有很强的非随机关联：共生体可能在一种蚜虫物种中很常见，但很少在近亲中发现。这表明宿主和微生物之间的动态相互作用可以在相对较短的进化时间尺度上驱动共生体的传播或损失。初步数据显示，寄主某些共生体会导致蚜虫体内关键免疫基因的表达急剧下降。这表明宿主免疫对共生关系的进化至关重要。该项目的主要目标是使用转录组测序和免疫分析来检验寄主免疫抑制是解释共生微生物在蚜虫物种中分布的关键机制这一假说。第二个目标是确定在容纳共生体和抵抗跨物种病原体的能力方面是否存在权衡。毒力和非毒力共生菌菌株的基因组也将使用一种新的共生体培养技术进行比较，以确定共生微生物致病的遗传特征。总之，这种跨物种的方法将改变我们对宿主免疫如何调节与共生微生物的关系的理解。因此，该项目将提供对无脊椎动物如何与微生物形成和维持关系的关键洞察，这些关系可以推动对粮食安全和健康至关重要的物种的快速适应性进化。这一美英合作项目得到了美国国家科学基金会和英国生物技术和生物科学研究委员会的支持。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Bacterial symbionts are widespread among animals and plants and often provide beneficial functions that profoundly influence their hosts' biology. Insects, in particular, have repeatedly formed symbioses with microbes for metabolism, nutrition, and protection. Insect immune systems are tasked with the challenge of controlling and regulating beneficial microbes while combating often closely-related pathogenic microbes. A critical unanswered question is whether the insect immune system is a key mediator of both symbionts and pathogens across different host species. This project will combine cutting edge genomics with experimental manipulations that will link immune responses with symbiont associations across diverse host species. Gaining a mechanistic understanding of how immune systems interact with symbionts is not only critical for understanding the evolution of host-associated microbiomes, it also has relevance to the invertebrate pests that vector devastating diseases of crops, livestock, and humans. In addition, there are research opportunities available for undergraduate students to train the next generation of STEM researchers.This project will use aphids as a model system and involves research at the University of Tennessee Knoxville and the Queen Mary University of London. Aphids are uniquely suited for this work because they have strong non-random associations with microbial symbionts: a symbiont species may be common in one aphid species, yet rarely found in a close relative. This suggests a dynamic interplay between host and microbe that can drive symbiont spread or loss over relatively short evolutionary timescales. Preliminary data has shown that hosting certain symbionts leads to a sharp decrease in the expression of key immune genes in aphids. This suggests host immunity is of central importance to the evolution of symbiotic relationships. The primary objective of this project is to use transcriptome sequencing and immune assays to test the hypothesis that host immune suppression is a key mechanism explaining the distribution of symbiotic microbes across aphid species. A secondary objective is to determine whether there is a trade-off in the ability to harbor symbionts and resist pathogens across species. Genomes of virulent and non-virulent symbiont strains will also be compared using a novel symbiont culturing technology to identify genetic features that underlie pathogenicity in symbiotic microbes. Together, this cross-species approach will transform our understanding of how host immunity moderates relationships with symbiotic microbes. This project will thus provide key insight into how invertebrates form and maintain relationships with microbes that can drive rapid adaptive evolution in species of central importance to food security and health. This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.