BBSRC-NSF/BIO - Host immune suppression as a key adaptation enabling bacterial symbioses

BBSRC-NSF/BIO - 宿主免疫抑制是实现细菌共生的关键适应

• 批准号: BB/W001632/1
• 负责人: Lee Henry
• 金额: $ 55.08万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW001632%2F1
• 关键词: BBSRC; NSF; BIO; Host; immune

Symbiotic microbes are increasingly being recognised as playing important roles in many aspects of plant and animal biology, for example in development, reproduction, immunity, nutrition, and defence. Yet we still have a limited understanding of what shapes the evolution of these important interactions, such as why one host species may establish a partnership with a given symbiont while a sister species does not. A key hypothesis is that the fate of many symbioses is determined by the properties of the host immune system. The immune system is tasked with the challenge of regulating beneficial microbes while combating often closely-related pathogens, which can cause devastating disease. However, the importance of the host immune system in mediating the evolution of symbiosis remains unclear. Invertebrates, in particular, have repeatedly formed symbioses with microbes for metabolism, resources, and protection. For example, the facultative symbionts of insects can expand their hosts' diet breadth or confer resistance to pathogens and pesticides, and drive rapid host evolution. What is striking about facultative symbionts is that they are not present in all species: a symbiont may be common in one host 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. Our pilot 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. Gaining a mechanistic understanding of how immune systems interact with symbionts is not only critical for understanding host-microbe evolution, it also has relevance to many invertebrates that commonly carry symbionts, including pest species that vector devastating diseases of crops, livestock and humans (e.g mosaic viruses, malaria). Understanding how host immunity shapes host-symbiont relationships is therefore highly relevant to BBSRC's priority research areas in sustainable agriculture and food security. The primary aim of our proposal is to test the hypothesis that host immune suppression is a key mechanism explaining the distribution of symbiotic microbes across insect species. Our second aim is to determine whether there is a trade-off in the ability to harbour symbionts and resist pathogens. Aphids are uniquely suited to meet these aims because they have strong non-random associations with symbionts: a symbiont species may be common in one aphid species, yet rarely found in a close relative. We will meet these aims in four Work Packages (WPs) that integrate cutting edge genomics with experimental manipulations that will link immune responses with symbiont associations across diverse host species. WP1 will determine whether host immune suppression is a mechanism allowing symbionts to establish in different host species. WP2 will establish if immune suppression impacts the costs, benefits or stability of symbioses. WP3 will reveal whether hosts trade-off in their ability to host symbionts and resist pathogens. Finally, WP4 will compare the genomes of virulent to non-virulent symbiont strains using a novel symbiont culturing technology to identify genetic features that underlie pathogenicity in symbiotic microbes. This will also provide key insights into whether symbionts, or hosts, are responsible for immune suppression. Together, our cross-species approach will transform our understanding of how host immunity moderates relationships with symbiotic microbes, which will have broad relevance across organisms. This includes many pest species of global importance in agriculture and medicine. Our proposal 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.

共生微生物越来越被认为在动植物生物学的许多方面起着重要作用，例如在发育，繁殖，免疫，营养和防御中发挥重要作用。然而，我们仍然对这些重要相互作用的演变的变化有限，例如为什么一个宿主物种可以与给定的共生体建立伙伴关系而姐妹物种却没有。一个关键的假设是，许多共生物的命运取决于宿主免疫系统的特性。免疫系统的任务是调节有益微生物的挑战，同时打击通常密切相关的病原体，这可能导致毁灭性疾病。但是，宿主免疫系统在介导共生进化中的重要性尚不清楚。 尤其是无脊椎动物，已经与微生物反复形成了新陈代谢，资源和保护的共生物。例如，昆虫的辅助共生体可以扩大其宿主的饮食广度或对病原体和农药的抗性，并推动快速宿主的进化。关于辅助共生体令人惊讶的是，它们在所有物种中都不存在：共生体在一个宿主物种中可能很常见，但在近亲中很少发现。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上驱动共生体扩散或损失。 我们的试点数据表明，托管某些共生体会导致蚜虫中关键免疫基因的表达急剧下降。这表明宿主免疫对于共生关系的演变至关重要。获得对免疫系统如何与共生体相互作用的机械理解不仅对于理解宿主微生物进化至关重要，而且还与许多通常携带共生物的无脊椎动物相关，包括携带虫害疾病的害虫物种，这些疾病是毁灭作物，牲畜，牲畜和人类的疾病（例如，摩西病毒病毒，疟疾，疟疾）。因此，了解宿主免疫如何形成宿主 - 与群岛的关系与BBSRC可持续农业和粮食安全方面的优先研究领域高度相关。 我们建议的主要目的是检验以下假设：宿主免疫抑制是解释共生微生物在昆虫物种中的分布的关键机制。我们的第二个目的是确定藏有共生体和抵抗病原体的能力是否有权衡。蚜虫非常适合满足这些目标，因为它们与共生体具有很强的非随机关联：共生物种在一个蚜虫物种中可能很常见，但在近亲中很少发现。 我们将在四个工作包（WPS）中达到这些目标，这些工作包（WPS）将最先进的基因组学与实验操作相结合，这些操作将将免疫反应与各种宿主物种之间的共生体关联起来。 WP1将确定宿主免疫抑制是否是允许共生体在不同宿主物种中建立的机制。 WP2将确定免疫抑制是否会影响共生的成本，收益或稳定性。 WP3将揭示主机在托管共生体和抵抗病原体的能力方面是否取舍。最后，WP4将使用一种新型的共生培养技术比较毒力到非毒气共生菌株的基因组，以鉴定共生微生物中致病性的遗传特征。这还将提供有关共生体或宿主是否负责免疫抑制的关键见解。共同，我们的跨物种方法将改变我们对宿主免疫如何与共生微生物之间的关系的理解，这将在生物体之间具有广泛的相关性。这包括许多在农业和医学中具有全球重要性的害虫。因此，我们的建议将提供有关如何形成无脊椎动物和与微生物的关系的关键见解，这些物种可以推动对粮食安全和健康的核心重要性的快速自适应发展。

项目成果

Variation in density, immune gene suppression, and coinfection outcomes among strains of the aphid endosymbiont Regiella insecticola

• DOI: 10.1093/evolut/qpad071
• 发表时间: 2023-05-08
• 期刊: EVOLUTION
• 影响因子: 3.3
• 作者: Goldstein, Elliott B.;de Anda Acosta, Yazmin;Parker, Benjamin J.
• 通讯作者: Parker, Benjamin J.