Date of Award

Winter 2006

Project Type

Thesis

Program or Major

Microbiology

Degree Name

Master of Science

First Advisor

Thomas G Pistole

Abstract

Apoptosis is an extremely important and highly regulated function in neutrophils. As the most abundant, but shortest-lived white blood cells, they must initiate this process in the absence of pathogens and selectively release their potent cytotoxic components when pathogens are present. Many pathogens are able to modulate this process in neutrophils, either for the host's benefit or for their own. Previous work has shown that transmigration across a T84 intestinal epithelial crypt cell monolayer increases the ability of neutrophils to bind and kill Salmonella enterica serovar Typhimurium (S. Typhimurium).

The goal of this work was to see how S. Typhimurium affects the cell death rate of human PMN. S. Typhimurium had little to no effect on inactivated neutrophils. When neutrophils were activated, either chemically through phorbol 12-myristate 13-acetate (PMA) or physiologically through transmigration, however, their normal apoptosis rate was delayed (p<0.0001). When S. Typhimurium was present at a ratio of ten bacteria to one neutrophil, apoptosis was significantly increased in these activated neutrophils more prominently when anaerobically grown (p=0.0027) compared to aerobically grown (p=.012).

Caspase-3 (p=0 .0129), but not -8 or -9, was associated with bacterial induced apoptosis in these studies. We conclude that S. Typhimurium modulates the rate of apoptosis in neutrophils, but only once these host cells have become activated. Our results provide further insights into the early events involved in Salmonella infections.

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