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Infection and Immunity, April 2002, p. 2070-2081, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2070-2081.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mice Lacking T and B Lymphocytes Develop Transient Colitis and Crypt Hyperplasia yet Suffer Impaired Bacterial Clearance during Citrobacter rodentium Infection

Bruce A. Vallance, Wanyin Deng, Leigh A. Knodler, and B. Brett Finlay*

Biotechnology Laboratory, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3

Received 5 June 2001/ Returned for modification 27 July 2001/ Accepted 14 December 2001

The bacterial pathogen Citrobacter rodentium belongs to a family of gastrointestinal pathogens that includes enteropathogenic and enterohemorrhagic Escherichia coli and is the causative agent of transmissible colonic hyperplasia in mice. The molecular mechanisms used by these pathogens to colonize host epithelial surfaces and form attaching and effacing (A/E) lesions have undergone intense study. In contrast, little is known about the host's immune response to these infections and its importance in tissue pathology and bacterial clearance. To address these issues, wild-type mice and mice lacking T and B lymphocytes (RAG1 knockout [KO]) were infected with C. rodentium. By day 10 postinfection (p.i.), both wild-type and RAG1 KO mice developed colitis and crypt hyperplasia, and these responses became more exaggerated in wild-type mice over the next 2 weeks, as they cleared the infection. By day 24 p.i., bacterial clearance was complete, and the colitis had subsided; however, crypt heights remained increased. In contrast, inflammatory and crypt hyperplastic responses in the RAG1 KO mice were transient, subsiding after 2 weeks. By day 24 p.i., RAG1 KO mice showed no signs of bacterial clearance and infection was often fatal. Surprisingly, despite remaining heavily infected, tissues from RAG1 KO mice surviving the acute colitis showed few signs of disease. These results thus emphasize the important contribution of the host immune response during infection by A/E bacterial pathogens. While T and/or B lymphocytes are essential for host defense against C. rodentium, they also mediate much of the tissue pathology and disease symptoms that occur during infection.

* Corresponding author. Mailing address: Biotechnology Laboratory, Room 237, Wesbrook Building, 6174 University Boulevard, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. Phone: 604-822-2210. Fax: 604-822-9830. E-mail: bfinlay{at}interchange.ubc.ca.

Editor: A. D. O'Brien

Infection and Immunity, April 2002, p. 2070-2081, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2070-2081.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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