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Science 319 (5864): 777-782

Copyright © 2008 by the American Association for the Advancement of Science

Innate Immune Homeostasis by the Homeobox Gene Caudal and Commensal-Gut Mutualism in Drosophila

Ji-Hwan Ryu,1* Sung-Hee Kim,1* Hyo-Young Lee,1,2 Jin Young Bai,1 Young-Do Nam,3 Jin-Woo Bae,3 Dong Gun Lee,4 Seung Chul Shin,1,5 Eun-Mi Ha,1 Won-Jae Lee1{dagger}

Abstract: Although commensalism with gut microbiota exists in all metazoans, the host factors that maintain this homeostatic relationship remain largely unknown. We show that the intestinal homeobox gene Caudal regulates the commensal-gut mutualism by repressing nuclear factor kappa B–dependent antimicrobial peptide genes. Inhibition of Caudal expression in flies via RNA interference led to overexpression of antimicrobial peptides, which in turn altered the commensal population within the intestine. In particular, the dominance of one gut microbe, Gluconobacter sp. strain EW707, eventually led to gut cell apoptosis and host mortality. However, restoration of a healthy microbiota community and normal host survival in the Caudal-RNAi flies was achieved by reintroduction of the Caudal gene. These results reveal that a specific genetic deficiency within a host can profoundly influence the gut commensal microbial community and host physiology.

1 Division of Molecular Life Science, Ewha Woman's University and National Creative Research Initiative Center for Symbiosystem, Seoul 120-750, South Korea.
2 Laboratoire de BBMI, Institut Pasteur, Paris 75724, France.
3 Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
4 School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701, South Korea.
5 Brain Korea 21 Program, Yonsei University College of Medicine, CPO Box 8044, Seoul 120-752, South Korea.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: lwj{at}ewha.ac.kr

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