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Infection and Immunity, June 1999, p. 3031-3039, Vol. 67, No. 6
Department of Paediatric Gastroenterology,
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
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

+. 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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