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A Mesh–Duox pathway regulates homeostasis in the insect gut

Nature Microbiology volume 2, Article number: 17020 (2017) Cite this article

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Abstract

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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Figure 1: Mesh maintains gut microbiome homeostasis by controlling AaDuox expression in A. aegypti.
Figure 2: Regulation of commensal microbiome and DmDuox expression in the guts of DmMesh RNAi Drosophila.
Figure 3: Mesh regulates AaDuox expression via Arrestin-mediated MAPK phosphorylation in A. aegypti.
Figure 4: Role of the Mesh-Arrestin-ERK/JNK-MAPK signalling cascade in DmDuox regulation in Drosophila.
Figure 5: AaMesh-mediated AaDuox regulatory pathway in response to commensal bacteria in the guts of A. aegypti.
Figure 6: DmMesh-mediated DmDuox regulation in response to commensal bacteria in Drosophila.

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Acknowledgements

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).

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Author notes

  1. Xiaoping Xiao, Lijuan Yang and Xiaojing Pang: These authors contributed equally to this work.

Authors and Affiliations

  1. Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China

    Xiaoping Xiao, Lijuan Yang, Xiaojing Pang, Rudian Zhang, Yibin Zhu, Guanjun Gao & Gong Cheng

  2. Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China

    Xiaoping Xiao, Xiaojing Pang & Gong Cheng

  3. SZCDC-SUSTech Joint Key Laboratory for Tropical Diseases, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, Guangdong, China

    Xiaoping Xiao & Gong Cheng

  4. Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, 511436, China

    Xiaoping Xiao

  5. School of Life Sciences, Tsinghua University, Beijing, 100084, China

    Lijuan Yang, Rudian Zhang, Yibin Zhu & Guanjun Gao

  6. College of Animal Science, Tarim University, Xinjiang, 843300, China

    Lijuan Yang

  7. Department of Microbiology and Immunology, School of Medicine, New York Medical College, Valhalla, 10595, New York, USA

    Penghua Wang

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Contributions

G.C. designed the experiments and wrote the manuscript. X.X. performed the majority of the experiments and analysed data. X.P., R.Z. and Y.Z. helped with RNA isolation and qPCR detection. L.Y. and G.G. provided the Drosophila systems and contributed to the investigations in Drosophila. P.W. contributed experimental suggestions and strengthened the writing of the manuscript. All authors reviewed, critiqued and provided comments to the text.

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Correspondence to Guanjun Gao or Gong Cheng.

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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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