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A recent study, led by Anaísa V Ferreira (Department of Internal Medicine) and Juan Carlos Alarcon-Barrera (Leiden University Medical Center), has shed new light on the role of fatty acid desaturation and lipid mediators in immune responses. The research groups, led by Martin Giera (Center for Proteomics and Metabolomics, Leiden University Medical Center) and Mihai Netea (Department of Internal Medicine), published the study in Nature Communications on 15th November 2023.
Lipid mediators are bioactive signalling molecules produced through the oxidation of polyunsaturated fatty acids by the action of different enzymes. The selective engagement of these oxidative pathways allows for the tailored production of lipid mediators in distinct inflammatory contexts. Some vaccines induce a long-term non-specific increase in responsiveness to subsequent stimulations. This phenomenon is characteristic of innate immune memory, also known as trained immunity.
The researchers found that lipid mediators contribute to the establishment of innate immune memory induced by the tuberculosis vaccine BCG. Human monocytes exposed to BCG in vitro were enriched for lipid mediators derived from the activity of lipoxygenases. Likewise, monocytes isolated from BCG vaccinated healthy individuals presented increased concentrations of 12-lipoxygenase-derived lipid mediators. Using pharmacological and genetic approaches, the researchers highlighted that lipoxygenase-derived lipid mediators play a key role in BCG-induced innate immune memory.
The exploration of lipid metabolic pathways contributes to the understanding of innate immune memory and may aid in the design of therapeutic tools and targets for the long-term modulation of innate immune responses.
The researchers plan to further investigate the complex immune regulation of lipid mediators during innate immune memory and their potential therapeutic applications.
Read the study here
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. Fatty acid desaturation and lipoxygenase pathways support trained immunity. Nature Communications; Published: November 15th, 2023; DOI: 10.1038/s41467-023-43315-
