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Infection and Immunity, June 1999, p. 3031-3039, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Citrobacter rodentium Infection in Mice Elicits a Mucosal Th1 Cytokine Response and Lesions Similar to Those in Murine Inflammatory Bowel Disease

Lisa M. Higgins,1 Gad Frankel,2 Gill Douce,2 Gordon Dougan,2 and Thomas T. MacDonald1,*

Department of Paediatric Gastroenterology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, St. Bartholomew's Hospital, London EC1A 7BE,1 and Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AZ,2 United Kingdom

Received 23 December 1998/Returned for modification 24 February 1999/Accepted 30 March 1999

Citrobacter rodentium is a classically noninvasive pathogen of mice that is similar to enteropathogenic Escherichia coli (EPEC) in man. Following oral infection of young mice, the organism colonizes the distal colon, and within 1 week the colonic mucosa doubles in thickness and there is massive epithelial cell hyperplasia. Since T-cell responses in mouse models of inflammatory bowel disease (IBD) also cause epithelial hyperplasia, we have investigated the possibility that C. rodentium promotes similar T-cell responses in the mucosa, thereby increasing epithelial shedding, transmission, and replication of the organism. Beginning 6 days after infection, bacteria were observed to be in close association with the epithelial surface and were also visible scattered throughout the lamina propria and in the submucosa. There was a CD3+-cell infiltrate into the colonic lamina propria and epithelium as well as mucosal thickening and crypt hyperplasia. The majority of CD3+ cells were CD4+ and were not gamma delta +. Reverse transcription-PCR analysis of cytokines also revealed a highly polarized Th1 response (interleukin-12, gamma interferon, and tumor necrosis factor alpha) in the mucosa and a large increase in the epithelial cell mitogen keratinocyte growth factor. None of the changes were seen in mice inoculated with bacteria lacking intimin (which is necessary for colonization), but they were seen in mice inoculated with C. rodentium complemented with intimin from EPEC. This is the first example of a classically noninvasive bacterial pathogen which elicits a strong mucosal Th1 response and which produces pathology similar to that seen in mouse models of IBD, which is also characterized by a strong Th1 response. These results also suggest that the colonic mucosa responds in a stereotypic way to Th1 responses.

* Corresponding author. Mailing address: Department of Paediatric Gastroenterology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Suite 31, Dominion House, 59 Bartholomew Close, London EC1A 7BE, United Kingdom. Phone: 44(0)171 601 8160. Fax: 44(0)171 600 5901. E-mail: t.t.macdonald{at}mds.qmw.ac.uk.

Infection and Immunity, June 1999, p. 3031-3039, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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  • Luperchio, S. A., Newman, J. V., Dangler, C. A., Schrenzel, M. D., Brenner, D. J., Steigerwalt, A. G., Schauer, D. B. (2000). Citrobacter rodentium, the Causative Agent of Transmissible Murine Colonic Hyperplasia, Exhibits Clonality: Synonymy of C. rodentium and Mouse-Pathogenic Escherichia coli. J. Clin. Microbiol. 38: 4343-4350 [Abstract] [Full Text]  
  • Hartland, E. L., Huter, V., Higgins, L. M., Goncalves, N. S., Dougan, G., Phillips, A. D., MacDonald, T. T., Frankel, G. (2000). Expression of Intimin gamma from Enterohemorrhagic Escherichia coli in Citrobacter rodentium. Infect. Immun. 68: 4637-4646 [Abstract] [Full Text]  
  • Vallance, B. A., Finlay, B. B. (2000). Exploitation of host cells by enteropathogenic Escherichiacoli. Proc. Natl. Acad. Sci. USA 97: 8799-8806 [Abstract] [Full Text]  
  • Caradonna, L., Amati, L., Magrone, T., Pellegrino, N.M., Jirillo, E., Caccavo, D. (2000). Invited review: Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. Innate Immunity 6: 205-214 [Abstract]  
  • Higgins, L. M., Frankel, G., Connerton, I., Gonçalves, N. S., Dougan, G., MacDonald, T. T. (1999). Role of Bacterial Intimin in Colonic Hyperplasia and Inflammation. Science 285: 588-591 [Abstract] [Full Text]  


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