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Published Online January 24, 2008
Science DOI: 10.1126/science.1149357

Research Articles

Submitted on August 17, 2007
Accepted on December 21, 2007

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

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

1 Division of Molecular Life Science, Ewha Woman’s University and National Creative Research Initiative Center for Symbiosystem, Seoul 120-750, South Korea.
2 Division of Molecular Life Science, Ewha Woman’s University and National Creative Research Initiative Center for Symbiosystem, Seoul 120-750, South Korea.; 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 Division of Molecular Life Science, Ewha Woman’s University and National Creative Research Initiative Center for Symbiosystem, Seoul 120-750, South Korea.; Brain Korea 21 Program, Yonsei University College of Medicine, CPO Box 8044, Seoul 120-752, South Korea.

* To whom correspondence should be addressed.
Won-Jae Lee , E-mail: lwj{at}ewha.ac.kr

{dagger}These authors contributed equally to this work.

Although commensalism with gut microbiota exists in all metazoans, the host factors that maintain this homeostatic relationship remain largely unknown. Here, we show that the intestinal homeobox gene Caudal regulates the commensal-gut mutualism by repressing NF-{kappa}B-dependent antimicrobial peptide genes. Inhibition of Caudal expression in flies using RNAi led to AMP overexpression, which in turn altered the commensal population within the intestine. In particular, 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 Cad gene. These results reveal that a specific genetic deficiency within a host can profoundly influence the gut commensal microbial community and host physiology.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)