CD3+ T Cell: CD14+ Monocyte Complexes Are Associated with Sugar-Derived Metabolites 3607

Abstract Description CD3+ T cell:CD14+ monocyte complexes form immunologic synapses contributing to inflammatory responses. These complexes are increased in people living with HIV (PLWH) with glucose intolerance. We hypothesized that alterations in plasma metabolites and lipids may have a role in maintaining these complexes. Using mass cytometry, we analyzed 36 markers in peripheral blood mononuclear cells from 38 PLWH (14 without diabetes, 24 with pre-diabetes/diabetes). We also measured fasting plasma metabolites and lipid compounds by untargeted metabolomics. Statistical analyses (Spearman Rank correlation) revealed that both circulating CD4+ T cell: and CD8+ T cell:CD14+ monocyte complexes were positively correlated with sugar-derived metabolites including glucosamine (ρ = 0.61, p < 0.0001), galactosamine (ρ = 0.60, p < 0.0001), glucuronic acid (ρ = 0.41, p = 0.01), and gluconate (ρ = 0.46, p = 0.004), and negatively correlated with the amino acids l-arginine (ρ=-0.59, p = 0.0001), l-lysine (ρ=-0.44, p = 0.006), l-glutamine (ρ=-0.52, p = 0.0008), and l-histidine (ρ=-0.51, p = 0.001). CD4+ T cell:CD14+ monocyte complexes also correlated with triacylglycerols (ρ = 0.47, p = 0.007). These findings highlight a potential role of circulating sugar metabolites in supporting CD3+ T cell:CD14+ monocyte complex formation. The findings could guide the optimization of vaccination strategies by harnessing these interactions in acute immune responses and provide insights into management of chronic inflammation in metabolic conditions Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)