Macrophages (MΦs) are prevalent innate immune cells, present throughout human bodily tissues where they orchestrate innate and adaptive immune responses to maintain cellular homeostasis. MΦs have the capacity to display a wide array of functional phenotypes due to different microenvironmental cues, particularly soluble bacterial secretory products. Recent evidence has emerged demonstrating that metabolism supports MΦ function and plasticity, in addition to energy and biomolecular precursor production. In this study, 1D ¹H-NMR-based metabolomics was used to identify the metabolic pathways that are differentially altered following primary human monocyte-derived MΦ exposure to P. aeruginosa planktonic- and biofilm-conditioned media (PCM and BCM). Metabolic profiling of PCM- and BCM-exposed MΦs indicated a significant increase in glycolytic metabolism, purine biosynthesis, and inositol phosphate metabolism. In addition, these metabolic patterns suggested that BCM-exposed MΦs exhibit a hyperinflammatory metabolic profile with reduced glycerol metabolism and elevated catabolism of lactate and amino acids, relative to PCM-exposed MΦs. Altogether, our study reveals novel findings concerning the metabolic modulation of human MΦs after exposure to secretory microbial products and contributes additional knowledge to the field of immunometabolism in MΦs.

中文翻译：

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铜绿假单胞菌浮游和生物膜条件培养基引发人类巨噬细胞的离散代谢反应

巨噬细胞 (MΦ) 是普遍存在的先天免疫细胞，存在于人体组织中，它们在其中协调先天和适应性免疫反应以维持细胞稳态。由于不同的微环境线索，特别是可溶性细菌分泌产物，MΦs 能够显示出广泛的功能表型。最近的证据表明，除了能量和生物分子前体的产生外，新陈代谢还支持 MΦ 功能和可塑性。在这项研究中，基于 1D ¹ H-NMR 的代谢组学用于鉴定在原代人类单核细胞衍生的 MΦ 暴露于铜绿假单胞菌后发生差异性改变的代谢途径浮游和生物膜条件培养基（PCM 和 BCM）。PCM 和 BCM 暴露的 MΦ 的代谢谱表明糖酵解代谢、嘌呤生物合成和肌醇磷酸代谢显着增加。此外，这些代谢模式表明，相对于 PCM 暴露的 MΦ，BCM 暴露的 MΦ 表现出高炎症代谢特征，甘油代谢减少，乳酸和氨基酸的分解代谢升高。总而言之，我们的研究揭示了关于人类 MΦ 在暴露于分泌性微生物产物后代谢调节的新发现，并为 MΦ 的免疫代谢领域贡献了更多的知识。