Date of Award

1994

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Animal Science (Animal, Dairy, and Poultry Sciences)

First Advisor

Theron G. Snider, III

Abstract

The resistance and immunologic responses of a Bcg susceptible (C57BL/6) and Bcg resistant (C3H/He) strain of mouse were compared after infection with Mycobacterium paratuberculosis. Bacterial resistance was evaluated by bacterial counts and histopathology of chronically infected mice. Levels of non-specific macrophage activation and the response of various T cell subsets were also evaluated following infection. Susceptible mice orally infected with Mycobacterium paratuberculosis developed granulomatous lesions containing acid-fast bacteria in the mesenteric lymph nodes. Significant differences in CFU of M. paratuberculosis were observed between C57BL/6 and C3H/He mice following an i.p. infection. Susceptible mice failed to limit bacterial proliferation, while bacterial counts progressively declined in resistant mice. Susceptible mice had numerous granulomas in the liver and developed mesenteric lymph node lesions. Resistant mice had fewer hepatic granulomas and did not develop mesenteric lymph node lesions. Both strains of mice developed similar levels of non-specific macrophage activation 10 days after i.p. infection with M. paratuberculosis as determined by a listeria challenge assay. Differences were detected in the proportions of T cell subsets and activation markers between the two strains. Both control and infected C3H/He mice had higher percentages of CD4+ cells, whereas C57BL/6 mice had higher proportions of CD8+ and $\gamma\delta$ cells. Both strains responded to the initial infection with increased numbers of CD8+ and/or $\gamma\delta$ cells, but resistant mice responded with higher proportions of CD4+ cells, whereas C57BL/6 mice responded with higher percentages of $\gamma\delta$ T and/or CD8+ cells. Differences in the expression of CD25+ and CD44+ cells were also detected between the two strains of mice. Expression of CD25 increased in resistant mice, but decreased in susceptible mice after infection. Overall CD44 expression was higher in susceptible mice but increased after infection in both mice. These data suggest that resistance to M. paratuberculosis is associated with higher proportions of CD4+ T cells, while CD8+ and/or $\gamma\delta$ T cells are associated with susceptibility. The decrease in CD25 receptor expression in susceptible mice suggests that a dysregulation in IL-2 or its receptor may also be involved in the pathogenesis of paratuberculosis.

Pages

199

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