Host Peroxisome Proliferator-Activated Receptors Play an Important Role During Coxiella burnetii Infection
Date of Award
8-2024
Degree Type
Thesis
Degree Name
Master of Science in Biomedical Sciences
First Advisor
Minal Mulye, PhD
Second Advisor
Ruth C. Borghaei, PhD
Third Advisor
Brian Balin, PhD
Abstract
The obligate intracellular bacterium Coxiella burnetii is transmitted to humans via inhalation and causes Q fever. Chronic Q fever often leads to endocarditis, which can develop years after the initial infection, indicating the bacterium's ability to survive long-term. While the host cell pathways Coxiella targets remain unknown, our lab has shown that Coxiella manipulates lipid storage organelles called lipid droplets (LDs) in alveolar macrophages. LD breakdown is essential for bacterial growth, and releases precursors for the immunosuppressive prostaglandin E2 (PGE2). LD breakdown-mediated PGE2 production is important for Coxiella intracellular survival, but whether Coxiella targets host transcriptional regulation to mediate these effects is not yet known. Peroxisome proliferator-activated receptors (PPARs) are transcription factors essential for macrophage LD metabolism and immune modulation, and contribute to the pathogenesis of intracellular microbes. Hence, we hypothesize that host PPARs play an important role in the intracellular survival of the bacterium Coxiella burnetii. To identify the importance of the PPAR subtypes—α, β/δ, and γ—during Coxiella infection, we measured bacterial growth in cells treated with subtype-specific PPAR agonists and antagonists. Notably, altering PPARα and β/δ activity decreased Coxiella growth. Blocking PPARα activity reduced host LD numbers and PGE2 concentrations, suggesting the importance of PPARα in promoting Coxiella survival. Our study establishes the role of host PPARs, specifically PPARα, during Coxiella infection. Future studies will explore PPARs as potential therapeutic targets to inhibit Coxiella intracellular growth.
Recommended Citation
O’Boyle, Kaitlin C., "Host Peroxisome Proliferator-Activated Receptors Play an Important Role During Coxiella burnetii Infection" (2024). PCOM Biomedical Studies Student Scholarship. 237.
https://digitalcommons.pcom.edu/biomed/237