Host immune suppression as a key adaptation enabling bacterial symbioses

细菌共生体广泛存在于动物和植物中，通常提供有益的功能，深刻地影响其宿主的生物学。尤其是昆虫，为了新陈代谢、营养和保护，它们反复与微生物形成共生关系。昆虫的免疫系统面临着控制和调节有益微生物的挑战，同时也在与通常密切相关的致病微生物作斗争。一个关键的悬而未决的问题是，昆虫免疫系统是否是跨不同宿主物种的共生体和病原体的关键媒介。该项目将结合尖端基因组学和实验操作，将免疫反应与不同宿主物种的共生关系联系起来。了解免疫系统如何与共生体相互作用不仅对理解宿主相关微生物群的进化至关重要，而且与传播作物、牲畜和人类毁灭性疾病的无脊椎害虫有关。此外，本科生也有研究机会培养下一代STEM研究人员。该项目将使用蚜虫作为模型系统，并涉及田纳西大学诺克斯维尔分校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：一种共生体可能在一种蚜虫中很常见，但在其近亲中却很少发现。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内驱动共生传播或损失。初步数据表明，寄存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。该项目的主要目的是利用转录组测序和免疫分析来验证宿主免疫抑制是解释共生微生物在蚜虫物种之间分布的关键机制的假设。第二个目标是确定在跨物种的共生和抵抗病原体的能力之间是否存在权衡。还将使用一种新的共生培养技术来比较有毒和非有毒共生菌株的基因组，以确定共生微生物致病性的遗传特征。总之，这种跨物种方法将改变我们对宿主免疫如何调节与共生微生物关系的理解。因此，该项目将为无脊椎动物如何形成并维持与微生物的关系提供关键见解，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。这个英美合作项目由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支持。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.