title: Persistent infection with Crohn's disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis.
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.
authors.affiliation: Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Cherrie-Lee N
authors.initials: CL
authors.lastname: Small
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Reid-Yu
authors.forename: Joseph B
authors.initials: JB
authors.lastname: McPhee
authors.forename: Brian K
authors.initials: BK
authors.lastname: Coombes
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D058491:Bacterial Load; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002432:Cecum / Q000382:microbiology / Q000473:pathology; D002452:Cell Count; D002908:Chronic Disease; D003106:Colon / Q000382:microbiology / Q000473:pathology; D003424:Crohn Disease / Q000150:complications / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D004926:Escherichia coli / Q000502:physiology*; D004927:Escherichia coli Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D007422:Intestines / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D012333:RNA, Messenger