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.
| Original language | English |
|---|---|
| Pages (from-to) | 651-63 |
| Number of pages | 13 |
| Journal | Cell Host & Microbe |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 11 May 2016 |
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- Journal Article
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Defensive Mutualism Rescues NADPH Oxidase Inactivation in Gut Infection. / Pircalabioru, Gratiela; Aviello, Gabriella; Kubica, Malgorzata; Zhdanov, Alexander; Paclet, Marie-Helene; Brennan, Lorraine; Hertzberger, Rosanne; Papkovsky, Dmitri; Bourke, Billy; Knaus, Ulla G.
In: Cell Host & Microbe, Vol. 19, No. 5, 11.05.2016, p. 651-63.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Defensive Mutualism Rescues NADPH Oxidase Inactivation in Gut Infection
AU - Pircalabioru, Gratiela
AU - Aviello, Gabriella
AU - Kubica, Malgorzata
AU - Zhdanov, Alexander
AU - Paclet, Marie-Helene
AU - Brennan, Lorraine
AU - Hertzberger, Rosanne
AU - Papkovsky, Dmitri
AU - Bourke, Billy
AU - Knaus, Ulla G
N1 - We thank B. Vallance, P. Cossart, and P. O’Toole for reagents; D. Guttman, S. Donaldson, and A. Surendra for microbiota sequencing and bioinformatics analysis; and the staff of the UCD Biomedical facility for their assistance. The work was supported by Science Foundation Ireland (U.G.K. and D.P.) and the National Children’s Research Center (U.G.K. and B.B.).
PY - 2016/5/11
Y1 - 2016/5/11
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.chom.2016.04.007
DO - 10.1016/j.chom.2016.04.007
M3 - Article
C2 - 27173933
VL - 19
SP - 651
EP - 663
JO - Cell Host & Microbe
JF - Cell Host & Microbe
SN - 1931-3128
IS - 5
ER -