biostudies-literatureFerreira AVFundação para a Ciência e TecnologiaEuropean Research Council7385https://www.ebi.ac.uk/biostudies/studies/S-EPMC10651900biostudies-literatureUnknown14(1)Infections and vaccines can induce enhanced long-term responses in innate immune cells, establishing an innate immunological memory termed trained immunity. Here, we show that monocytes with a trained immunity phenotype, due to exposure to the Bacillus Calmette-Guérin (BCG) vaccine, are characterized by an increased biosynthesis of different lipid mediators (LM) derived from long-chain polyunsaturated fatty acids (PUFA). Pharmacological and genetic approaches show that long-chain PUFA synthesis and lipoxygenase-derived LM are essential for the BCG-induced trained immunity responses of human monocytes. Furthermore, products of 12-lipoxygenase activity increase in monocytes of healthy individuals after BCG vaccination. Grasping the underscoring lipid metabolic pathways contributes to our understanding of trained immunity and may help to identify therapeutic tools and targets for the modulation of innate immune responses.Nature communicationsFatty acid desaturation and lipoxygenase pathways support trained immunity.PMC10651900833247Ziogas ATerschlusen EGiamarellos-Bourboulis EJAlarcon-Barrera JCOzhan HNRenieris GBulut OKilic GFerreira AVDebisarun PAKostidis SGiera MRoring RJMatzaraki VDominguez-Andres JMohammed YNetea MGfalseFatty acid desaturation and lipoxygenase pathways support trained immunity.Infections and vaccines can induce enhanced long-term responses in innate immune cells, establishing an innate immunological memory termed trained immunity. Here, we show that monocytes with a trained immunity phenotype, due to exposure to the Bacillus Calmette-Guérin (BCG) vaccine, are characterized by an increased biosynthesis of different lipid mediators (LM) derived from long-chain polyunsaturated fatty acids (PUFA). Pharmacological and genetic approaches show that long-chain PUFA synthesis and lipoxygenase-derived LM are essential for the BCG-induced trained immunity responses of human monocytes. Furthermore, products of 12-lipoxygenase activity increase in monocytes of healthy individuals after BCG vaccination. Grasping the underscoring lipid metabolic pathways contributes to our understanding of trained immunity and may help to identify therapeutic tools and targets for the modulation of innate immune responses.2023-01-01T00:00:00Z2023 Nov2026-06-18T06:47:35.375Z2025-04-19T16:14:23.663ZS-EPMC106519003796831310.1038/s41467-023-43315-x