Fatty acid desaturation and lipoxygenase pathways support trained immunity

Anaísa V. Ferreira (), Juan Carlos Alarcon-Barrera, Jorge Domínguez-Andrés, Özlem Bulut, Gizem Kilic, Priya A. Debisarun, Rutger J. Röring, Hatice N. Özhan, Eva Terschlüsen, Athanasios Ziogas, Sarantos Kostidis, Yassene Mohammed, Vasiliki Matzaraki, George Renieris, Evangelos J. Giamarellos-Bourboulis, Mihai G. Netea and Martin Giera ()
Additional contact information
Anaísa V. Ferreira: Radboud University Nijmegen Medical Center
Juan Carlos Alarcon-Barrera: Leiden University Medical Center
Jorge Domínguez-Andrés: Radboud University Nijmegen Medical Center
Özlem Bulut: Radboud University Nijmegen Medical Center
Gizem Kilic: Radboud University Nijmegen Medical Center
Priya A. Debisarun: Radboud University Nijmegen Medical Center
Rutger J. Röring: Radboud University Nijmegen Medical Center
Hatice N. Özhan: Radboud University Nijmegen Medical Center
Eva Terschlüsen: Radboud University Medical Centre
Athanasios Ziogas: Radboud University Nijmegen Medical Center
Sarantos Kostidis: Leiden University Medical Center
Yassene Mohammed: Leiden University Medical Center
Vasiliki Matzaraki: Radboud University Nijmegen Medical Center
George Renieris: National and Kapodistrian University of Athens, Medical School
Evangelos J. Giamarellos-Bourboulis: National and Kapodistrian University of Athens, Medical School
Mihai G. Netea: Radboud University Nijmegen Medical Center
Martin Giera: Leiden University Medical Center

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-43315-x

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