Basic–Alimentary TractChronic Enteric Salmonella Infection in Mice Leads to Severe and Persistent Intestinal Fibrosis
Section snippets
Mice
129SvJ mice15 were bred in the Animal Unit at the University of British Columbia (UBC). 129Sv/ImJ, DBA2, and C3H/HeOuJ mice (Jackson Laboratories, Bar Harbor, ME) were infected at an age of 8–12 weeks. Mice were given 20 mg of streptomycin orally 24 hours prior to infection with 3 × 106 or 3 × 108 bacteria in 100 μL HEPES buffer (100 mmol/L, pH 8.0) by oral gavage. All animal experiments were conducted consistent with the ethical requirements of the Animal Care Committee at UBC.
Bacterial Strains
S Typhimurium
Chronic Infection With S Typhimurium Induces Inflammation and Tissue Pathology
Pretreatment with the antibiotic streptomycin facilitates S Typhimurium infection of the murine GI tract.13 129Sv/J mice were treated with streptomycin 24 hours prior to infection with 3 × 106S Typhimurium and killed at specific time points thereafter. By day 7 postinfection (pi), the ceca and colons of infected mice were heavily colonized, with the pathogen burden ranging from 105 to 109Salmonella in these tissues (Figure 1A), which is in line with previous studies.14 Colonization of all
Discussion
Intestinal fibrosis and stricture formation are among the most problematic clinical features of CD, in large part because they are strikingly resistant to anti-inflammatory treatments. As a result, therapeutic options are limited, with endoscopic balloon dilatation usually only delaying intervention with stricturoplasty or surgical resection of affected segments. Although the etiology underlying the development of intestinal fibrosis remains unknown, commensal bacteria and/or bacterial products
References (37)
- et al.
Mouse models for the study of Crohn’s disease
Trends Mol Med
(2003) - et al.
Chronic intestinal inflammation: an unexpected outcome in cytokine or T cell receptor mutant mice
Cell
(1993) - et al.
Hapten-induced model of chronic inflammation and ulceration in the rat colon
Gastroenterology
(1989) - et al.
A murine model of chronic inflammation-induced intestinal fibrosis down-regulated by antisense NF-κB
Gastroenterology
(2003) Crohn’s disease
Lancet
(2002)- et al.
Animal models of mucosal inflammation and their relation to human inflammatory bowel disease
Curr Opin Immunol
(1999) A mouse model of intestinal fibrosis?
Gastroenterology
(2003)- et al.
Collagen content and types in the intestinal strictures of Crohn’s disease
Gastroenterology
(1988) - et al.
Discovering the cause of inflammatory bowel disease: lessons from animal models
Curr Opin Gastroenterol
(2000) - et al.
Lessons from genetically engineered animal models XINovel mouse models to study pathogenic mechanisms of Crohn’s disease
Am J Physiol Gastrointest Liver Physiol
(2000)
Lessons from genetic models of inflammatory bowel disease
Acta Gastroenterol Belg
Medical therapy for Crohn’s disease strictures
Inflamm Bowel Dis
Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts
Am J Physiol
FibrogenesisIV. Fibrosis and inflammatory bowel disease: cellular mediators and animal models
Am J Physiol Gastrointest Liver Physiol
TGF-β1 gene transfer to the mouse colon leads to intestinal fibrosis
Am J Physiol Gastrointest Liver Physiol
Induction of a fibrogenic response in mouse colon by overexpression of monocyte chemoattractant protein 1
Gut
Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host
Infect Immun
Chronic Salmonella enterica serovar Typhimurium-induced colitis and cholangitis in streptomycin-pretreated Nramp1+/+ mice
Infect Immun
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Supported by CIHR (to B.A.V. and B.B.F.) and Genome Canada (to B.B.F.); by postdoctoral fellowships from the Michael Smith Foundation for Health Research (MSFHR), Genome Canada, and the Deutsche Forschungsgemeinschaft (to G.A.G.); and by a doctoral fellowship from MSFHR (to K.S.B.B.).
The authors thank Caixia Ma, Tina Huang, and Lisa Thorson for excellent technical assistance; Erin Boyle, Kelly McNagny, Kevan Jacobson, Michael Blennerhassett, and members of the Finlay lab for critical comments on the manuscript; and Carrie Rosenberger and Alan Aderem for kindly providing the flagellin mutant.
Conflicts of interest: No conflicts of interest exist.
- 1
B.A.V. is the CHILD Foundation Research Scholar, the Canada Research Chair in Pediatric Gastroenterology, and an MSFHR Scholar.
- 2
B.B.F. is a CIHR Distinguished Investigator, an HHMI International Research Scholar, and the UBC Peter Wall Distinguished Professor.
- 3
G.A.G. and Y.V. contributed equally to this work.
- 4
B.A.V. and B.B.F. are co-senior authors.