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ETD RECORD
Human innate immune cell function and response to Yersinia expressing a functional TTSS and effector Yops
Citation
Spinner, Justin.. (2009). Human innate immune cell function and response to Yersinia expressing a functional TTSS and effector Yops. Theses and Dissertations Collection, University of Idaho Library Digital Collections. https://www.lib.uidaho.edu/digital/etd/items/etd_371.html
- Title:
- Human innate immune cell function and response to Yersinia expressing a functional TTSS and effector Yops
- Author:
- Spinner, Justin.
- Date:
- 2009
- Keywords:
- Yersinia pestis--Genetic aspects
- Program:
- Microbiology, Molecular Biology, and Biochemistry
- Abstract:
- The human innate immune system is reliant upon the coordinated activity of macrophages and polymorphonuclear leukocytes (neutrophils or PMNs) for recognition and elimination of invading pathogens. Yersinia spp. are renowned for their ability to subvert the innate immune system and cause disease in humans. Y. pestis, in particular, is a human pathogen of historical and current significance which relies on the activity of injected virulence plasmid encoded effector Yop proteins, via a type III secretion system, into host immune system cells to evade clearance by the immune system. The activity of Yops within murine macrophages and dendritic cells has been investigated; however, the activity of Yops within human polymorphonuclear leukocytes (neutrophils or PMNs) has not been directly examined. Herein, the coordinated activity of Y. pestis virulence plasmid encoded Yops on isolated human PMNs is explored. Specifically, the role of Yops in evasion of isolated human PMN phagocytosis, ROS production, killing, and induction of apoptosis is described. Y. pestis was found to inhibit isolated human PMN phagocytosis in a virulence plasmid dependent manner. However, a substantial number of Y. pestis are initially phagocytosed. Phagocytosed bacteria were killed by PMNs regardless of virulence plasmid dependent inhibition of reactive oxygen species (ROS) production, but there was a population of Y. pestis which survived inside the PMN independent of the presence of the virulence plasmid. Although Y. pestis inhibition of ROS did not directly impact the fate of intracellular bacteria, analysis of PMN cell death following incubation with virulence plasmid containing Y. pestis revealed that PMNs are not induced to undergo YopJ/YopP dependent caspase activation and apoptosis as in macrophages. The absence of the virulence plasmid actually resulted in greater PMN lysis following apoptosis. This suggests that, Yersinia ROS inhibition limits fulminate isolated human PMN apoptosis after phagocytosis.
- Description:
- Thesis (Ph. D., Microbiology, Molecular Biology and Biochemistry)--University of Idaho, May 2009.
- Major Professor:
- Gustavo Arrizabalaga.
- Defense Date:
- May 2009.
- Type:
- Text
- Format Original:
- xiv, 142 leaves :ill. (some col.) ;29 cm.
- Format:
- record
Rights
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