Date of Award

4-3-2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Microbiology & Immunology

First Advisor

David Bradley

Abstract

This study demonstrates that 2 month old, female B10.T(6R) are highly resistant to systemic infection with the KIM5 strain of Yersinia pestis , and that B10.T(6R) mice become susceptible to Y. pestis infection by 5 months of age. In this study we infected both young (2 month) and middle-aged (5-12 month) B10.T(6R) with equal CFUs of Y. pestis. LD50 of young B10.T(6R) was ∼1.4 X 10 4 CFU, while middle-aged B10. T(6R) mice exhibited an LD50 of ∼60 CFU. An elevated bacterial burden was found in the spleens of middle-aged mice at 24 and 60 h and the livers at 60 h postinfection. Immune cell infiltration was greater in the livers of resistant young mice as compared to middle-aged and the susceptible C57BL6/N strain of mice. Unlike susceptible mice, young B10.T(6R) did not develop necrotic lesions throughout the liver. Instead young B10.T(6R) livers contained granulomatous-like structures. Immunohistochemical staining of liver sections from these mice at 60 h postinfection revealed that the majority of immune cells present in these structures consisted of neutrophils. Elevated levels of proinflammatory mediators were found in the sera and spleens of susceptible mice. However, IL-1β levels were increased in young B10.T(6R) mice both in vivo and in vitro . These findings suggest that resistance to plague correlates with early formation of neutrophilic lesions in the liver and increased IL-1β levels may contribute to resistance.

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