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Science 310 (5749): 847-850

Copyright © 2005 by the American Association for the Advancement of Science

A Direct Role for Dual Oxidase in Drosophila Gut Immunity

Eun-Mi Ha,1 Chun-Taek Oh,2 Yun Soo Bae,1 Won-Jae Lee1,2*

Abstract: Because the mucosal epithelia are in constant contact with large numbers of microorganisms, these surfaces must be armed with efficient microbial control systems. Here, we show that the Drosophila nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme, dual oxidase (dDuox), is indispensable for gut antimicrobial activities. Adult flies in which dDuox expression is silenced showed a marked increase in mortality rate even after a minor infection through ingestion of microbe-contaminated food. This could be restored by the specific reintroduction of dDuox, demonstrating that this oxidase generates a unique epithelial oxidative burst that limits microbial proliferation in the gut. Thus, oxidant-mediated antimicrobial responses are not restricted to the phagocytes, but rather are used more broadly, including in mucosal barrier epithelia.

1 Division of Molecular Life Science and Center for Cell Signaling Research, Ewha Woman's University, Seoul 120-750, South Korea.
2 Laboratory of Innate Immunity, Institut Pasteur Korea, Seoul 136-791, South Korea.

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

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »

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