Adherence Affects Monocyte Innate Immune Function and Metabolic Reprogramming after Lipopolysaccharide Stimulation In Vitro

Abstract Circulating nonadherent monocytes can migrate to extravascular sites by a process that involves adherence. Alterations in intracellular metabolism shape the immunological phenotype of phagocytes upon activation. To determine effect adherence on their metabolic and functional response human were stimulated with LPS under adherent conditions. Adherent (relative monocytes) produced less TNF IL-1? (proinflammatory) more IL-10 (anti-inflammatory) stimulation had an increased capacity phagocytose produce reactive oxygen species. RNA sequencing analysis confirmed modified LPS-induced monocytes, reducing expression proinflammatory genes involved TLR signaling increasing induction pathogen elimination. Adherence resulted glycolytic as indicated lactate release, gene set enrichment, [13C]-glucose flux analysis. role glycolysis immune responses, this pathway was inhibited glucose deprivation or analogue 2-deoxy-d-glucose (2DG). Although both interventions equally glycolysis, only 2DG influenced monocyte functions, inhibiting elimination, well cytokine release. 2DG, but not deprivation, reduced oxidative phosphorylation. Inhibition phosphorylation affected release similar way 2DG. Collectively, these data suggest may modify profile inhibition phosphorylation, alone, has profound functions exposed LPS.