title: Defensive Mutualism Rescues NADPH Oxidase Inactivation in Gut Infection.
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.
authors.affiliation: Conway Institute, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Gratiela
authors.initials: G
authors.lastname: Pircalabioru
authors.affiliation: National Children's Research Center, Our Lady's Children's Hospital Crumlin, Dublin 12, Ireland.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Aviello
authors.affiliation: Conway Institute, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kubica
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork T12 YN60, Ireland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zhdanov
authors.affiliation: Institut de Biologie et Pathologie, Centre Hospitalier Universitaire de Grenoble, Grenoble 3809, France.
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Paclet
authors.affiliation: School of Agriculture and Food Science, University College Dublin, Dublin 4, Ireland.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Brennan
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Rosanne
authors.initials: R
authors.lastname: Hertzberger
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork T12 YN60, Ireland.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Papkovsky
authors.affiliation: National Children's Research Center, Our Lady's Children's Hospital Crumlin, Dublin 12, Ireland.
authors.forename: Billy
authors.initials: B
authors.lastname: Bourke
authors.affiliation: Conway Institute, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland; National Children's Research Center, Our Lady's Children's Hospital Crumlin, Dublin 12, Ireland. Electronic address: ulla.knaus@ucd.ie.
authors.forename: Ulla G
authors.initials: UG
authors.lastname: Knaus
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000378:metabolism*; D064806:Dysbiosis; D004756:Enterobacteriaceae Infections / Q000201:enzymology* / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006105:Granulomatous Disease, Chronic / Q000382:microbiology; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007778:Lactobacillus; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000172:deficiency / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013559:Symbiosis
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases