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

人们越来越认识到共生微生物在动植物生物学的许多方面发挥着重要作用，例如在发育、繁殖、免疫、营养和防御方面。然而，我们对这些重要的相互作用的进化过程的理解仍然有限，比如为什么一个宿主物种可能与一个给定的共生体建立伙伴关系，而一个姊妹物种却没有。一个关键的假设是，许多共生的命运是由宿主免疫系统的特性决定的。免疫系统肩负着调节有益微生物的挑战，同时也要与可能导致毁灭性疾病的密切相关的病原体作斗争。然而，宿主免疫系统在介导共生进化中的重要性仍不清楚。特别是无脊椎动物，为了新陈代谢、资源和保护，与微生物反复形成共生关系。例如，昆虫的兼性共生体可以扩大寄主的饮食范围，或赋予寄主对病原体和杀虫剂的抵抗力，并推动寄主的快速进化。兼性共生体的惊人之处在于它们并非存在于所有物种中：共生体可能在一个宿主物种中很常见，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。我们的试点数据表明，寄存某些共生体导致蚜虫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。了解免疫系统如何与共生体相互作用不仅对理解宿主-微生物进化至关重要，而且与许多通常携带共生体的无脊椎动物有关，包括传播作物、牲畜和人类毁灭性疾病的害虫物种（如花叶病毒、疟疾）。因此，了解宿主免疫如何塑造宿主-共生体关系与BBSRC在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验证宿主免疫抑制是解释共生微生物在昆虫物种之间分布的关键机制的假设。我们的第二个目标是确定在庇护共生体和抵抗病原体的能力之间是否存在权衡。蚜虫特别适合满足这些目标，因为它们与共生体有很强的非随机联系：共生体物种可能在一种蚜虫中很常见，但在近亲中却很少发现。我们将在四个工作包（WPs）中实现这些目标，这些工作包将尖端基因组学与实验操作相结合，将免疫反应与不同宿主物种的共生关联联系起来。WP1将决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将揭示寄主是否在寄主共生体和抵抗病原体的能力之间进行权衡。最后，WP4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。这也将为共生体或宿主是否负责免疫抑制提供关键见解。总之，我们的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，这将在整个生物体中具有广泛的相关性。这包括许多对农业和医药具有全球重要性的害虫物种。因此，我们的建议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。

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.