Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
Nat Microbiol. 2017 Mar 1;2:17020. doi: 10.1038/nmicrobiol.2017.20.
The metazoan gut harbours complex communities of commensal and symbiotic bacterial microorganisms. The quantity and quality of these microorganisms fluctuate dynamically in response to physiological changes. The mechanisms that hosts have developed to respond to and manage such dynamic changes and maintain homeostasis remain largely unknown. Here, we identify a dual oxidase (Duox)-regulating pathway that contributes to maintaining homeostasis in the gut of both Aedes aegypti and Drosophila melanogaster. We show that a gut-membrane-associated protein, named Mesh, plays an important role in controlling the proliferation of gut bacteria by regulating Duox expression through an Arrestin-mediated MAPK JNK/ERK phosphorylation cascade. Expression of both Mesh and Duox is correlated with the gut bacterial microbiome, which, in mosquitoes, increases dramatically soon after a blood meal. Ablation of Mesh abolishes Duox induction, leading to an increase of the gut microbiome load. Our study reveals that the Mesh-mediated signalling pathway is a central homeostatic mechanism of the insect gut.
后生动物肠道中栖息着复杂的共生和共生细菌微生物群落。这些微生物的数量和质量会随生理变化而动态波动。宿主为应对和管理这种动态变化并维持体内平衡而发展的机制在很大程度上仍是未知的。在这里，我们鉴定出一种双氧化酶（Duox）调节途径，该途径有助于维持埃及伊蚊和黑腹果蝇肠道的体内平衡。我们发现一种定位于肠道膜的蛋白，命名为 Mesh，通过一种 Arrestin 介导的 MAPK JNK/ERK 磷酸化级联反应来调控 Duox 表达，从而在控制肠道细菌增殖方面发挥重要作用。Mesh 和 Duox 的表达与肠道细菌微生物组相关联，在蚊子中，该微生物组在饱餐一顿血液后会急剧增加。Mesh 的缺失会消除 Duox 的诱导，导致肠道微生物组负荷增加。我们的研究揭示了 Mesh 介导的信号通路是昆虫肠道的一个重要的体内平衡机制。
