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Coordination of multiple dual oxidase–regulatory pathways in responses to commensal and infectious microbes in drosophila gut

Nature Immunology volume 10, pages 949–957 (2009)Cite this article

Abstract

All metazoan guts are in permanent contact with the microbial realm. However, understanding of the exact mechanisms by which the strength of gut immune responses is regulated to achieve gut-microbe mutualism is far from complete. Here we identify a signaling network composed of complex positive and negative mechanisms that controlled the expression and activity of dual oxidase (DUOX), which 'fine tuned' the production of microbicidal reactive oxygen species depending on whether the gut encountered infectious or commensal microbes. Genetic analyses demonstrated that negative and positive regulation of DUOX was required for normal host survival in response to colonization with commensal and infectious microbes, respectively. Thus, the coordinated regulation of DUOX enables the host to achieve gut-microbe homeostasis by efficiently combating infection while tolerating commensal microbes.

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Figure 1: Regulation of Duox expression.
Figure 2: MEKK1-MKK3-p38-ATF2 as a Duox expression pathway.
Figure 3: PG-dependent Duox expression pathway.
Figure 4: PG-independent Duox expression pathway.
Figure 5: Negative regulation of the Duox expression pathway.
Figure 6: Negative or positive regulation of the Duox expression pathway is required for normal host survival in mutualistic or infectious gut-microbe interactions, respectively.

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Acknowledgements

We thank J. Chung (Korea Advanced Institute of Science and Technology) for fly stocks. Supported by the National Creative Research Initiative Program of the Korean Ministry of Education, Science and Technology, World Class University project (R31-2008-000-10010-0), Global Research Laboratory program (K20815000001 to B.-H.O.), and Brain Korea 21 project (E.-M.H., K.-A.L. and Y.Y.S.).

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Author notes

  1. Eun-Mi Ha and Kyung-Ah Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Life and Pharmaceutical Science, Ewha Woman's University, Seoul, South Korea

    Eun-Mi Ha, Kyung-Ah Lee, You Yeong Seo, Sung-Hee Kim, Jaesang Kim & Won-Jae Lee

  2. National Creative Research Initiative Center for Symbiosystem, Ewha Woman's University, Seoul, South Korea

    Eun-Mi Ha, Kyung-Ah Lee, You Yeong Seo, Sung-Hee Kim & Won-Jae Lee

  3. Beamline Division, Pohang Accelerator Laboratory, Pohang, Kyungbuk, South Korea

    Jae-Hong Lim

  4. Center for Biomolecular Recognition and Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, South Korea

    Byung-Ha Oh

  5. Department of Life Science, Ewha Woman's University, Seoul, 120-750, South Korea

    Jaesang Kim & Won-Jae Lee

  6. Department of Bioinspired Science, Ewha Woman's University, Seoul, 120-750, South Korea

    Won-Jae Lee

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Contributions

E.-M.H., K.-A.L., Y.Y.S., S.-H.K. and J.-H.L. did the experiments; W.-J.L. supervised the research; J.K. and B.-H.O. provided technical support; W.-J.L. sponsored the research; and E.-M.H., K.-A.L. and W.-J.L. prepared the manuscript.

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Correspondence to Won-Jae Lee.

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Ha, EM., Lee, KA., Seo, Y. et al. Coordination of multiple dual oxidase–regulatory pathways in responses to commensal and infectious microbes in drosophila gut. Nat Immunol 10, 949–957 (2009). https://doi.org/10.1038/ni.1765

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