Host immunological control of the gut microbiota during pupation

化蛹期间肠道微生物群的宿主免疫控制

• 批准号: 437264270
• 负责人: Professor Dr. Michael T. Monaghan, since 9/2023
• 金额: --
• 依托单位: Arbeitsgruppe Rolff - Evolutionsbiologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/437264270?language=en
• 关键词: Host; immunological; control; gut; microbiota

Immune effectors are best studied as defenses induced by microbial infections. However beyond simple immune defense they also play important roles in the regulation of host-microbe interactions. We will investigate how immune effectors can be repurposed for regulation of the gut microbiota during metamorphosis without compromising their utility as canonical immune defences by selecting for bacterial resistance. We will use the wax moth Galleria mellonella, which has a well characterized immune gene repertoire and is the basis of our established model of metamorphic gut immunity. Specifically, we will use RNAi knockdown to manipulate the number of immune effectors expressed in the metamorphic gut in order to (i) quantify the rate of bacterial resistance evolution towards combinations of up to 4 immune effectors, (ii) identify the underlying mechanisms of bacterial resistance and quantify their effects on resistance, cross-resistance, and collateral sensitivity, (iii) quantify the fitness costs of resistance evolution both in vitro and in vivo, and in the presence and absence of the gut microbiota. Thus we will test the hypothesis that the complexity of metamorphic gut immunity has evolved to exploit a combination of functionally distinct immune effectors that minimize the probability of resistance emergence in the presence of the gut microbiota. The results will show how the host is able to replace and recycle the midgut while simultaneously controlling the resident microbiota, a challenge posed by the evolution of complete metamorphosis and thus faced by all holometabolous insects.

免疫效应子最好作为由微生物感染诱导的防御来研究。然而，除了简单的免疫防御，它们还在调节宿主-微生物相互作用中发挥重要作用。我们将研究如何在变态过程中重新利用免疫效应子来调节肠道微生物群，而不会通过选择细菌抗性来损害它们作为典型免疫防御的效用。我们将使用蜡蛾Galleria mellonella，它具有良好的免疫基因库，并且是我们建立的变态肠道免疫模型的基础。具体地，我们将使用RNAi敲低来操纵在变态肠道中表达的免疫效应物的数量，以便（i）量化细菌对多达4种免疫效应物的组合的抗性进化的速率，（ii）鉴定细菌抗性的潜在机制并量化它们对抗性、交叉抗性和附带敏感性的影响，（iii）量化体外和体内以及在存在和不存在肠道微生物群的情况下的抗性进化的适应性成本。因此，我们将测试这样一个假设，即变态肠道免疫的复杂性已经进化到利用功能上不同的免疫效应物的组合，这些免疫效应物在肠道微生物群存在的情况下最大限度地降低了耐药性出现的可能性。结果将显示宿主如何能够在控制常驻微生物群的同时替换和回收中肠，这是完全变态进化所带来的挑战，因此所有全变态昆虫都面临着这一挑战。