engleski

Immunometabolic phenotype of BV-2 microglial cells upon cytomegalovirus infection

Microglia cells are resident macrophages in the brain, and possess key functions such as promoting development, maintaining synaptic and neuronal homeostasis. They are versatile cells that rapidly respond to both endogenous and exogenous stimuli. Cytomegalovirus is a pathogen linked to many disorders in the central nervous system followed by microglial activation. Studies have shown that microglial cells have a role in antiviral defense. The aim of our research was to determine the susceptibility and consequences of the murine cytomegalovirus infection on the BV-2 microglial cells. The experiments were performed on the immortalized BV-2 microglial cell line, a proven replacement for the primary microglia. Cells were cultivated in DMEM, with and without fetal calf serum supplementation to achieve a quiescent and ramified state. Light and immunofluorescent microscopy was used to study morphology and expression of cell phenotype markers (CD206, Arginase-1, iNOS, hypoxia inducible factor-1α). Western blot was used to detect viral infection markers IE-1 (immediate early infection marker) and m04 (late infection marker). Real-time metabolic status of the cells was studied using the Seahorse method. Features of infected cells were comparable in both cell- growth types. Infection of ramified BV-2 microglial cells altered their morphology from ramified to ameboid, while also altering the expression of M2 markers CD206 and Arginase-1 and the M1 marker iNOS. Expression of HIF-1α was increased in infected cells. Seahorse analysis revealed significantly higher metabolic activity in infected cells compared to the controls, especially in the rate of glycolysis. Microglia infected with murine cytomegalovirus have significantly altered immunologic and metabolic properties, inducing M1-like activation and aerobic glycolysis. Further research is required to determine whether these changes benefit the host or the virus and what is the pathophysiological mechanism behind these changes.

microglia ; cytomegalovirus ; immunometabolism

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