Randomized trial investigates metabolic changes in activated macrophages across different vertebrate species, suggesting unique responses to fever temperatures.
Introduction Response to fever affects the biological process in animals and often they are conserved in animals. In this study we investigate the role of activated macrophages in different vertebrate animal models- in homeothermic (chickens and mice) versus poikilothermic vertebrates (rainbow trout). Methods We use various cell lines from young adult mice cell line, RAW 264.7, chicken cell line HTC and rainbow trout splenic cells RTS 11; tissue macrophages from all three species and mouse bone marrow-derived macrophages (BMDM) to test metabolic changes, gene expression changes in response to fever using Greiss, qPCR, and Seahorse assays Results Stimulating cells with LPS, and IFN-g showed higher NO production, treatment with LPS and Interleukins (ILs) caused increase in iNOS mRNA levels. Metabolism increased during fever temperatures in all three species when glycolytic rates and oxidative phosphorylation rates were measured. Stimulation caused a reduction in OCR (rate of oxidative phosphorylation) and increase in PER (glycolysis) mice and chicken. For fish cells however, observations were strikingly different where unstimulated cells at fever temperatures showed higher metabolic activity, and with stimulation OXPHOS dominates and showed an early PER increase.ATP levels also showed an increase at fever temperatures when compared to the body temperatures for all three species. Conclusion Metabolism increased with fever temperatures in all three species. For Rainbow trout were much more engaged in OXPHOS. Funding Source Fulbright Immunology Fund Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)
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