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The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
11:04

The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis

Published on: February 19, 2013

A major role for proteolytic activity and proteinase-activated receptor-2 in the pathogenesis of infectious colitis

Kristina K Hansen1, Philip M Sherman, Laurie Cellars

  • 1Proteinases and Inflammation Network, Mucosal Inflammation Research Group, Department of Pharmacology, University of Calgary, Calgary, AB, Canada T2N 4N1.

Proceedings of the National Academy of Sciences of the United States of America
|May 28, 2005
PubMed

Insights

Bacterial infection causes inflammation by activating host serine proteinases and proteinase-activated receptor-2 (PAR2). Inhibiting these pathways reduces colitis severity in mice.

Area of Science:

  • Microbiology
  • Immunology
  • Gastroenterology

Background:

  • Citrobacter rodentium infection in mice models human enterohemorrhagic E. coli infections.
  • Infectious colitis involves complex host-pathogen interactions and inflammatory responses.

Purpose of the Study:

  • To investigate the role of host serine proteinases and proteinase-activated receptor-2 (PAR2) in Citrobacter rodentium-induced infectious colitis.

Main Methods:

  • Analysis of colonic luminal fluid from infected mice using mass spectrometry and Western blot.
  • Assessment of inflammatory indices including macroscopic damage, wall thickness, granulocyte infiltration, and bacterial translocation.
  • Evaluation of inflammation in wild-type mice treated with soybean trypsin inhibitor and in PAR2-deficient mice.

Main Results:

  • Active serine proteinases, including granzyme A and murine trypsins, were detected in the colonic luminal fluid of infected mice.
  • Increased inflammatory indices were observed in C. rodentium-infected mice compared to controls.
  • Treatment with soybean trypsin inhibitor or the absence of PAR2 significantly reduced C. rodentium-induced inflammation.

Conclusions:

  • Pathogen-induced host serine proteinases play a significant role in infectious colitis.
  • Proteinase-activated receptor-2 (PAR2) is critically involved in mediating inflammation during C. rodentium infection.
  • Targeting host serine proteinases and PAR2 may offer therapeutic strategies for infectious colitis.

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