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Defensive Mutualism Rescues NADPH Oxidase Inactivation in Gut Infection

Gratiela Pircalabioru1, Gabriella Aviello2, Malgorzata Kubica1

  • 1Conway Institute, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

Cell Host & Microbe
|May 14, 2016
PubMed

Insights

Mice lacking Cyba in the gut epithelium showed increased protective bacteria and resistance to infection. This suggests a novel gut defense mechanism involving reactive oxygen species (ROS) and the microbiome.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • The NOX/DUOX family of NADPH oxidases are key producers of reactive oxygen species (ROS).
  • Intestinal epithelial NOX1, NOX4, and DUOX2 functions remain unclear.
  • Cyba (p22(phox)) is an essential dimerization partner for NOX enzymes.

Purpose of the Study:

  • To investigate the role of Cyba in the intestinal epithelium.
  • To understand the impact of epithelial Cyba deficiency on ROS production and host defense against enteric pathogens.

Main Methods:

  • Generated mice with complete or epithelium-restricted Cyba deficiency.
  • Assessed epithelial reactive oxygen species (ROS) levels.
  • Performed infection models with Citrobacter rodentium and Listeria monocytogenes.
  • Analyzed gut microbiota composition.

Main Results:

  • Epithelial Cyba deficiency led to magnified epithelial ROS deficiency, regulated by NOX1-DUOX2 interaction.
  • Mice lacking epithelial Cyba exhibited enhanced protection against C. rodentium and L. monocytogenes.
  • Gut microbiota analysis revealed an enrichment of hydrogen peroxide (H2O2)-producing bacteria, particularly lactobacilli.
  • Elevated lactobacilli levels suppressed C. rodentium virulence via H2O2-mediated inhibition of the LEE pathogenicity island.

Conclusions:

  • Epithelial Cyba deficiency confers protection against enteric infections through a microbiota-dependent mechanism.
  • This involves an enrichment of H2O2-producing bacteria that attenuate pathogen virulence.
  • This transmissible, environmentally influenced adaptation offers insights into enteric disease prevention and therapy.

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