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.
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This work was funded by grants from the National Key Research and Development Plan of China (2016YFD0500400, 2016YFC1201000 and 2016ZX10004001-008), grants from the National Natural Science Foundation of China (81422028, 81571975, 61472205, 31171278 and 31271542) and a grant from the US National Institutes of Health (AI103807). The authors thank W.-J. Lee from Seoul National University for providing Erwinia carotovora carotovora 15 for the study. The authors thank G.K. Christophides from Imperial College London for providing critical suggestions for this manuscript. G.C. is a Newton Advanced Fellow (awarded by the Academy of Medical Sciences and the Newton Fund) and a Janssen Investigator of Tsinghua University. The authors acknowledge technical support from the Core Facility of the Center for Life Sciences and Center of Biomedical Analysis (Tsinghua University).
The authors declare no competing financial interests.
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Xiao, X., Yang, L., Pang, X. et al. A Mesh–Duox pathway regulates homeostasis in the insect gut. Nat Microbiol 2, 17020 (2017). https://doi.org/10.1038/nmicrobiol.2017.20
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