Coxiella Burnetii Infection Increases Cyclooxygenase Levels in Alveolar Macrophages
Minal Mulye Ph.D
Medicine and Health Sciences
Coxiella burnetii is a Gram-negative obligate intracellular pathogen, which spreads via inhalation. Although it initially infects alveolar macrophages, it can cause endocarditis several months to years after infection. This suggests that Coxiella has the ability to survive long-term within the host cells. Our overall goal is to identify how Coxiella achieves this long-term intracellular survival. Previous studies suggest that Coxiella manipulates host lipid metabolism and immune response to establish infection. Our lab has recently shown that Coxiella specifically manipulates metabolism of host lipid storage organelles called lipid droplets (LDs). Further, blocking LD breakdown inhibits bacterial growth suggesting that LD-derived lipids are critical for Coxiella growth. On breakdown, LDs release arachidonic acids, which are converted to prostaglandin E2 (PGE2) by the enzyme cyclooxygenase (COX). PGE2 modulates immune responses during alveolar macrophage infection by other intracellular pathogens like M. tuberculosis, C. pneumoniae to promote bacterial survival. Hence we hypothesize that in Coxiella-infected cells lipid droplet breakdown results in increased PGE2 production to promote bacterial growth. To test this hypothesis, we first analyzed the gene expression of PGE2 synthesis enzyme COX. Compared to uninfected cells, we observed increased cox expression in Coxiella-infected cells. Further, quantitation of total COX enzymatic activity using a fluorescence assay showed increased total COX activity in Coxiella-infected cells. Since COX levels are directly proportional to PGE2 production, our data suggests that Coxiella infection increases PGE2 levels. Ongoing studies are identifying the role of lipid droplets in PGE2 production and the importance of PGE2 during Coxiella infection.
Copyright 2018 all authors
Leeds, Blake OMS-2 and Mulye, Minal Ph.D, "Coxiella Burnetii Infection Increases Cyclooxygenase Levels in Alveolar Macrophages" (2018). MU-COM Research Day. 89.