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Defensive Mutualism Rescues NADPH Oxidase Inactivation in Gut Infection
- Source :
- Cell hostmicrobe. 19(5)
- Publication Year :
- 2015
-
Abstract
- NOX/DUOX family of NADPH oxidases are expressed in diverse tissues and are the primary enzymes for the generation of reactive oxygen species (ROS). The intestinal epithelium expresses NOX1, NOX4, and DUOX2, whose functions are not well understood. To address this, we generated mice with complete or epithelium-restricted deficiency in the obligatory NOX dimerization partner Cyba (p22(phox)). We discovered that NOX1 regulates DUOX2 expression in the intestinal epithelium, which magnified the epithelial ROS-deficiency. Unexpectedly, epithelial deficiency of Cyba resulted in protection from C. rodentium and L. monocytogenes infection. Microbiota analysis linked epithelial Cyba deficiency to an enrichment of H2O2-producing bacterial strains in the gut. In particular, elevated levels of lactobacilli physically displaced and attenuated C. rodentium virulence by H2O2-mediated suppression of the virulence-associated LEE pathogenicity island. This transmissible compensatory adaptation relied on environmental factors, an important consideration for prevention and therapy of enteric disease.
- Subjects :
- 0301 basic medicine
Virulence
NADPH Oxidase
Biology
Granulomatous Disease, Chronic
Microbiology
03 medical and health sciences
Mice
0302 clinical medicine
Intestinal mucosa
Virology
medicine
Animals
Intestinal Mucosa
Symbiosis
Lactobacillu
chemistry.chemical_classification
Reactive oxygen species
NADPH oxidase
Animal
Enterobacteriaceae Infections
NOX4
NADPH Oxidases
medicine.disease
Enterobacteriaceae Infection
Intestinal epithelium
Dysbiosi
Gastrointestinal Microbiome
Mice, Inbred C57BL
Lactobacillus
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
NOX1
Immunology
cardiovascular system
biology.protein
Citrobacter rodentium
Dysbiosis
Parasitology
Reactive Oxygen Specie
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 19346069
- Volume :
- 19
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cell hostmicrobe
- Accession number :
- edsair.doi.dedup.....60489ebe3af6e3ee6819f43fc7c691fe