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Infection and Immunity, November 2009, p. 4983-4989, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00627-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Ce-Duox1/BLI-3 Generates Reactive Oxygen Species as a Protective Innate Immune Mechanism in Caenorhabditis elegans{triangledown}

Violeta Chávez, Akiko Mohri-Shiomi,{dagger} and Danielle A. Garsin*

Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, Houston, Texas 77030

Received 2 June 2009/ Returned for modification 6 July 2009/ Accepted 8 August 2009

Caenorhabditis elegans was recently developed as a model system to study both pathogen virulence mechanisms and host defense responses. We previously demonstrated that C. elegans produces reactive oxygen species (ROS) in response to exposure to the important gram-positive nosocomial pathogen Enterococcus faecalis. We also presented evidence of oxidative stress and upregulation of stress responses after exposure to the pathogen. As in mammalian systems, this new work shows that production of ROS for innate immune functions occurs via an NADPH oxidase. Specifically, reducing expression of a dual oxidase, Ce-Duox1/BLI-3, causes a decrease in ROS production in response to E. faecalis. We also present evidence that reduction of expression of Ce-Duox1/BLI-3 increases susceptibility to this pathogen, specifically when expression is reduced in the intestine and the hypodermis. Ce-Duox1/BLI-3 was previously characterized as having a role in cuticle cross-linking. Two C. elegans mutants with point mutations in the peroxidase domain that exhibit severe cuticle defects were discovered to be unaffected in ROS production or pathogen susceptibility. These results demonstrate an important biological role for the peroxidase domain in cuticle cross-linking that is unrelated to ROS production. To further demonstrate the protective effects of the pathogen-induced ROS production, we show that antioxidants that scavenge ROS increase the sensitivity of the nematode to the infection, in stark contrast to their longevity-promoting effects under nonpathogenic conditions. In conclusion, we postulate that the generation of ROS by NADPH oxidases in the barrier epithelium is an ancient, highly conserved innate immune defense mechanism.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, 6431 Fannin St./MSB 1.168, Houston, TX 77030. Phone: (713) 500-5454. Fax: (713) 500-5499. E-mail: Danielle.A.Garsin{at}uth.tmc.edu

{triangledown} Published ahead of print on 17 August 2009.

Editor: A. Camilli

{dagger} Present address: Division of Brain Function, Department of Integrated Genetics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.

Infection and Immunity, November 2009, p. 4983-4989, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00627-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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