Persistent infection with Crohn’s disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis

Cherrie-Lee N. Small, Sarah A. Reid-Yu, Joseph B. McPhee and Brian K. Coombes ()
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Cherrie-Lee N. Small: Michael G. DeGroote Institute for Infectious Disease Research, McMaster University
Sarah A. Reid-Yu: Michael G. DeGroote Institute for Infectious Disease Research, McMaster University
Joseph B. McPhee: Michael G. DeGroote Institute for Infectious Disease Research, McMaster University
Brian K. Coombes: Michael G. DeGroote Institute for Infectious Disease Research, McMaster University

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract in which alterations to the bacterial community contribute to disease. Adherent-invasive Escherichia coli are associated with human Crohn’s disease; however, their role in intestinal immunopathology is unclear because of the lack of an animal model compatible with chronic timescales. Here we establish chronic adherent-invasive Escherichia coli infection in streptomycin-treated conventional mice (CD1, DBA/2, C3H, 129e and C57BL/6), enabling the study of host response and immunopathology. Adherent-invasive Escherichia coli induces an active T-helper 17 response, heightened levels of proinflammatory cytokines and fibrotic growth factors, with transmural inflammation and fibrosis. Depletion of CD8+ T cells increases caecal bacterial load, pathology and intestinal fibrosis in C57BL/6 mice, suggesting a protective role. Our findings provide evidence that chronic adherent-invasive Escherichia coli infections result in immunopathology similar to that seen in Crohn’s disease. With this model, research into the host and bacterial genetics associated with adherent-invasive Escherichia coli-induced disease becomes more widely accessible.

Date: 2013
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DOI: 10.1038/ncomms2957

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