R-spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea

Olivier Papapietro1, Sarah Teatero, Ajitha Thanabalasuriar

  • 1Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4.

Insights

R-spondin2 gene identified as key to susceptibility in Citrobacter rodentium infection. Its induction causes Wnt-driven proliferation, leading to immature colons and severe diarrhea in mice.

Area of Science:

  • Microbiology
  • Immunology
  • Genetics

Background:

  • Citrobacter rodentium is a mouse model for human E. coli infections.
  • Susceptibility to C. rodentium infection is linked to genetic factors and physiological pathways.
  • Understanding these determinants is crucial for infectious diarrhea research.

Purpose of the Study:

  • To identify genetic determinants of susceptibility to Citrobacter rodentium infection.
  • To elucidate the role of Wnt signaling in infectious colitis.

Main Methods:

  • Forward genetic screen in mice.
  • Analysis of gene expression during infection.
  • Assessment of colonic epithelium differentiation and function.

Main Results:

  • R-spondin2 gene identified as a major determinant of susceptibility.
  • Infection induces R-spondin2 expression in susceptible mice.
  • R-spondin2 drives Wnt-mediated crypt cell proliferation, resulting in immature colonic epithelium.

Conclusions:

  • R-spondin2 and Wnt signaling play a critical role in susceptibility to infectious diarrhea.
  • R-spondin2 is a key molecular link between infection and intestinal homeostasis.
  • This study uncovers a novel mechanism of host-pathogen interaction.

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