Host Peroxisome Proliferator-Activated Receptor Alpha is Essential for Coxiella burnetii Intracellular Survival and Prostaglandin E2 Production 2307362

Abstract Introduction The obligate intracellular bacterium Coxiella burnetii causes Q fever, often leading to chronic endocarditis, which reflects the bacterium’s capacity for long-term survival within host cells. Our research shows that Coxiella manipulates host lipid storage organelles, known as lipid droplets (LDs), in alveolar macrophages. The breakdown of these LDs is crucial for bacterial growth, as it releases precursors necessary for the production of the immunosuppressive molecule, prostaglandin E2 (PGE2). This LD breakdown-mediated PGE2 production is essential for Coxiella survival, but the host transcriptional mechanisms mediating this process have been unclear. We hypothesized that host Peroxisome Proliferator-Activated Receptors (PPARs)–transcription factors vital for macrophage lipid metabolism and immune modulation–play a significant role in Coxiella intracellular survival. Methods To test this, we used subtype-specific PPAR agonists and antagonists and measured bacterial growth. Results We found that altering PPARα activity significantly decreased Coxiella growth. Furthermore, PPARα activation increased PGE2 concentrations, suggesting a direct link between PPARα and the promotion of Coxiella survival. Conclusion Our study indicates that host PPARα initiates a suppressive immune response to support Coxiella infection. These findings identify host PPARs as potential therapeutic targets to inhibit Coxiella intracellular growth. Funding Source N/A Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)