Mycobacterium avium Subspecies Paratuberculosis Triggers Intestinal Pathophysiologic Changes in Beige/Scid Mice
Abstract:We investigated whether infection of beige/scid mice with Mycobacterium avium subspecies paratuberculosis can induce intestinal pathophysiologic changes. Six-week-old beige/scid mice were inoculated intraperitoneally with M. paratuberculosis, then were killed 32 weeks after inoculation when the small intestine was evaluated for physiologic and morphologic abnormalities. All infected mice developed clinical disease. The lamina propria of the intestine from infected mice was mildly infiltrated with mononuclear cells containing acid-fast bacteria, and had significantly increased villus width. In vitro physiologic studies in Ussing chambers indicated that M. paratuberculosis infection caused significant abnormalities in intestinal transport parameters. Baseline short circuit current and potential difference were abnormally high in tissues from infected, compared with control mice, indicative of increased ion secretion. Baseline conductance was significantly decreased in infected mice, suggesting that intestinal tissue from infected mice was less permeable to ions. The change in short circuit current following transmural electrical and glucose stimulation was significantly reduced in intestines from infected mice, suggesting that inflamed intestine had neural and/or epithelial cell damage. We conclude that infection of beige/scid mice with M. paratuberculosis triggers significant intestinal pathophysiologic changes consistent with chronic inflammation. These functional abnormalities may contribute to the pathogenesis of the wasting syndrome seen in bovids with paratuberculosis. This animal model provides evidence that T cell-independent mechanisms are sufficient to cause mucosal pathophysiologic changes and inflammation in response to a specific pathogen, and may be of relevance to inflammatory bowel disease in humans.
Document Type: Research Article
Affiliations: 1: Departments of Pathobiology, University of Guelph, Guelph, Ontario Canada 2: Department of Pathology, McMaster University, Hamilton, Ontario, Canada 3: Clinical Studies, University of Guelph, Guelph, Ontario Canada
Publication date: December 1, 2001
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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