Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands.
Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313, Porto, Portugal.
Nat Commun. 2023 Nov 15;14(1):7385. doi: 10.1038/s41467-023-43315-x.
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.
感染和疫苗可诱导先天免疫细胞产生增强的长期反应，从而建立一种称为训练有素的免疫的先天免疫记忆。在这里，我们表明，由于接触卡介苗（BCG）疫苗，具有训练有素的免疫表型的单核细胞的特征是不同的衍生自长链多不饱和脂肪酸（PUFA）的脂质介质（LM）的生物合成增加。药理和遗传方法表明，长链 PUFA 合成和脂氧合酶衍生的 LM 对于人单核细胞中 BCG 诱导的训练有素的免疫反应是必需的。此外，在 BCG 疫苗接种后，健康个体的单核细胞中的 12-脂氧合酶活性产物增加。掌握基础脂质代谢途径有助于我们理解训练有素的免疫，并可能有助于确定调节先天免疫反应的治疗工具和靶标。
