Details

Autor(en) / Beteiligte

• Pircalabioru, Gratiela
• Aviello, Gabriella
• Kubica, Malgorzata
• Zhdanov, Alexander
• Paclet, Marie-Helene
• Brennan, Lorraine
• Hertzberger, Rosanne
• Papkovsky, Dmitri
• Bourke, Billy
• Knaus, Ulla G.

Titel

Defensive Mutualism Rescues NADPH Oxidase Inactivation in Gut Infection

Ist Teil von

• Cell host & microbe, 2016-05, Vol.19 (5), p.651-663

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• 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 (p22phox). 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. [Display omitted] •The NADPH oxidase NOX1 regulates DUOX2 expression during intestinal infection•Cyba (p22phox)-deficiency, inactivating NOX1–4, is protective in enteric infection•Loss of epithelial NOX activity promotes enrichment of H2O2-producing gut commensals•Commensal-derived H2O2 is a negative regulator of LEE virulence factors in Citrobacter The three-way relationship between host-produced reactive oxygen species (ROS), gut microbiota, and enteric pathogens is unexplored. Pircalabioru et al. demonstrate in mice that in the absence of epithelial ROS, compensatory adaptation of the microbiota confers protection against enteric pathogens by fostering H2O2-producing commensals, which act by downregulating virulence factors.