Dissertation
Characterizing the duration of Coxiella burnetii shedding and the genetic influence behind a key immune effector cell
Washington State University
Doctor of Philosophy (PhD), Washington State University
01/2021
DOI:
https://doi.org/10.7273/000002413
Handle:
https://hdl.handle.net/2376/120858
Abstract
Coxiella burnetii is a bacterial pathogen distributed around the globe that causes disease in both animals and humans. Humans can develop a syndrome called “Q fever”, characterized by a flulike syndrome or pneumonia and hepatitis in the acute phase and by potentially fatal endocarditis or vascular infection in some chronic cases. Sheep and goats infected with C. burnetii can suffer clusters of fetal loss that, via aerosol from birth fluids and the placenta, are a major source of infection for humans. The infectious dose in humans is as low as one bacterium, and the organism is hardy in the environment. On a cellular level, C. burnetii preferentially infects macrophages, a cell type derived in many cases from circulating monocytes, and macrophages are considered important in both the survival and clearance of C. burnetii infection. To better understand and control this transmission cycle, we sought to characterize the infection in sheep both by observing shedding in the natural setting and by conducting a genome-wide association with absolute monocyte counts in sheep blood. In chapter one, we measure prevalence to antibodies against C. burnetii (seroprevalence) and shedding by multiple routes on a large sheep farm that had been associated with a human transmission event of Q fever three decades prior. Our findings demonstrate no detectable levels of C. burnetii by polymerase chain reaction and a seroprevalence similar to that of the average large sheep farm in the United States, challenging a previously held assumption that infection persists indefinitely once established on a premises. Our discussion speculates on reasons shedding may have ceased in the absence of targeted intervention and considers the implications of this finding. In chapter two, we perform a genome-wide association with absolute counts of circulating monocytes in sheep. Several significant sites are discovered, and the regions for which they are predictive includes genes involved in hematopoiesis, macrophage activation, and monocyte differentiation. The results have implications for genetic influences on an important effector cell in C. burnetii infection. Together, these data shed light on both the natural transmission cycle and possible immunologic genes involved in infection.
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Details
- Title
- Characterizing the duration of Coxiella burnetii shedding and the genetic influence behind a key immune effector cell
- Creators
- Ryan Oliveira
- Contributors
- Stephen White (Advisor)Holly Neibergs (Advisor)Massaro Ueti (Committee Member)Anders Omsland (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 78
- Identifiers
- 99900606753401842
- Language
- English
- Resource Type
- Dissertation