Coxiella burnetii infection upregulates enzyme cycloxygenase-2 gene expression in alveolar macrophages
Dr. Minal Mulye, Ph.D.
Medicine and Health Sciences
Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes Q fever in humans. While acute infection manifests as self-limiting flu-like illness, chronic Q fever presents as non-culturable endocarditis, which is fatal if untreated. Although Coxiella spreads via inhalation and initially infects alveolar macrophages, it survives in the host long-term and may spread to the heart and cause endocarditis. The occurrence of Coxiella endocarditis up to 20 years after initial infection suggests that the bacterium persists in the host and subverts several host cell processes to promote infection. Our overall goal is to identify specific host cell pathways that Coxiella manipulates to achieve long-term intracellular survival. Previous studies in Coxiella endocarditis patients reported increased production of the lipid immune mediator prostaglandin E2 (PGE2), which subsequently promoted Coxiella growth. Our preliminary studies in infected alveolar macrophages reveal an increase in PGE2 production, suggesting its importance during Coxiella infection. Hence, we hypothesize that targeting PGE2 production in Coxiella-infected cells prevents bacterial intracellular growth. Since PGE2 production is directly proportional to the expression and activity of the enzyme cyclooxygenases (Cox), we first determined the gene expression of constitutively expressed Cox-1 and infection-induced Cox-2. Our studies show that Coxiella infection increases Cox-2 gene expression and not Cox-1, suggesting the importance of Cox-2-derived PGE2 production in Coxiella-infected cells. Ongoing studies are determining Cox-2 enzymatic activity in infected cells. Future studies will deter-mine the potential of Cox-2 as a therapeutic target to prevent Coxiella's long-term survival and thus treat endocarditis.
Copyright 2019 all authors
Kim, Constantine OMS-2; Shain, Michael OMS-2; Wooten, Steven; and Mulye, Minal Ph.D, "Coxiella burnetii infection upregulates enzyme cycloxygenase-2 gene expression in alveolar macrophages" (2019). MU-COM Research Day. 156.