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R-Spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea

Author

Listed:
  • Olivier Papapietro

    (McGill University
    Complex Traits Program, McGill University)

  • Sarah Teatero

    (McGill University
    Complex Traits Program, McGill University)

  • Ajitha Thanabalasuriar

    (McGill University
    Complex Traits Program, McGill University)

  • Kyoko E. Yuki

    (Complex Traits Program, McGill University
    McGill University)

  • Eduardo Diez

    (McGill University
    Complex Traits Program, McGill University)

  • Lei Zhu

    (McGill University
    Complex Traits Program, McGill University)

  • Eugene Kang

    (McGill University
    Complex Traits Program, McGill University)

  • Sandeep Dhillon

    (SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children
    Institute of Medical Science, University of Toronto
    Hepatology, and Nutrition, University of Toronto, Hospital for Sick Children)

  • Aleixo M. Muise

    (SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children
    Institute of Medical Science, University of Toronto
    Hepatology, and Nutrition, University of Toronto, Hospital for Sick Children)

  • Yves Durocher

    (Biotechnology Research Institute, National Research Council of Canada)

  • Martin M. Marcinkiewicz

    (Cytochem Inc.)

  • Danielle Malo

    (Complex Traits Program, McGill University
    McGill University
    McGill University Health Center)

  • Samantha Gruenheid

    (McGill University
    Complex Traits Program, McGill University)

Abstract

Citrobacter rodentium is a natural mouse pathogen widely used as a model for enteropathogenic and enterohemorrhagic Escherichia coli infections in humans. While C. rodentium causes self-limiting colitis in most inbred mouse strains, it induces fatal diarrhoea in susceptible strains. The physiological pathways as well as the genetic determinants leading to susceptibility have remained largely uncharacterized. Here we use a forward genetic approach to identify the R-spondin2 gene as a major determinant of susceptibility to C. rodentium infection. Robust induction of R-spondin2 expression during infection in susceptible mouse strains causes a potent Wnt-mediated proliferative response of colonic crypt cells, leading to the generation of an immature and poorly differentiated colonic epithelium with deficiencies in ion-transport components. Our data demonstrate a previously unknown role of R-spondins and Wnt signalling in susceptibility to infectious diarrhoea and identify R-spondin2 as a key molecular link between infection and intestinal homoeostasis.

Suggested Citation

  • Olivier Papapietro & Sarah Teatero & Ajitha Thanabalasuriar & Kyoko E. Yuki & Eduardo Diez & Lei Zhu & Eugene Kang & Sandeep Dhillon & Aleixo M. Muise & Yves Durocher & Martin M. Marcinkiewicz & Danie, 2013. "R-Spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea," Nature Communications, Nature, vol. 4(1), pages 1-9, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2816
    DOI: 10.1038/ncomms2816
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