Journal article
Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in C. elegans
PLoS pathogens, Vol.7(12), pp.e1002453-e1002453
12/01/2011
DOI: 10.1371/journal.ppat.1002453
PMCID: PMC3245310
PMID: 22216003
Abstract
Infected animals will produce reactive oxygen species (ROS) and other inflammatory molecules that help fight pathogens, but can inadvertently damage host tissue. Therefore specific responses, which protect and repair against the collateral damage caused by the immune response, are critical for successfully surviving pathogen attack. We previously demonstrated that ROS are generated during infection in the model host Caenorhabditis elegans by the dual oxidase Ce-Duox1/BLI-3. Herein, an important connection between ROS generation by Ce-Duox1/BLI-3 and upregulation of a protective transcriptional response by SKN-1 is established in the context of infection. SKN-1 is an ortholog of the mammalian Nrf transcription factors and has previously been documented to promote survival, following oxidative stress, by upregulating genes involved in the detoxification of ROS and other reactive compounds. Using qRT-PCR, transcriptional reporter fusions, and a translational fusion, SKN-1 is shown to become highly active in the C. elegans intestine upon exposure to the human bacterial pathogens, Enterococcus faecalis and Pseudomonas aeruginosa. Activation is dependent on the overall pathogenicity of the bacterium, demonstrated by a weakened response observed in attenuated mutants of these pathogens. Previous work demonstrated a role for p38 MAPK signaling both in pathogen resistance and in activating SKN-1 upon exposure to chemically induced oxidative stress. We show that NSY-1, SEK-1 and PMK-1 are also required for SKN-1 activity during infection. Evidence is also presented that the ROS produced by Ce-Duox1/BLI-3 is the source of SKN-1 activation via p38 MAPK signaling during infection. Finally, for the first time, SKN-1 activity is shown to be protective during infection; loss of skn-1 decreases resistance, whereas increasing SKN-1 activity augments resistance to pathogen. Overall, a model is presented in which ROS generation by Ce-Duox1/BLI-3 activates a protective SKN-1 response via p38 MAPK signaling.
Details
- Title: Subtitle
- Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in C. elegans
- Creators
- Ransome van der Hoeven - The University of Texas Health Science Center at HoustonKatie C. McCallum - The University of Texas Health Science Center at HoustonMelissa R. Cruz - The University of Texas Health Science Center at HoustonDanielle A. Garsin - The University of Texas Health Science Center at Houston
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.7(12), pp.e1002453-e1002453
- DOI
- 10.1371/journal.ppat.1002453
- PMID
- 22216003
- PMCID
- PMC3245310
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Publisher
- Public Library Science
- Number of pages
- 14
- Grant note
- NIH National Center for Research Resources (NCRR); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AI076406 / National Institute of Allergy and Infectious Diseases at the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01AI076406 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 12/01/2011
- Academic Unit
- Dental Research; Periodontics
- Record Identifier
- 9984738106102771
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