Fig. 3: Lactate is a physiologic fuel for trained immunity.

a–f Monocytes were cultured in MM containing ¹³C-glucose (5 mM), indicating unlabeled lactate concentration, and treated with β-glucan (5 μg/ml) for 4 hrs, followed by mass spectrometry analyzes. g Schematic of derivation and contribution of carbon atoms in SAM synthesis. h Experiments were performed as described in (a). ¹³C-glucose labeling into ATP or SAM is shown. i Monocytes were treated with β-glucan and lactate (1 mM) for 30 min; mitochondrial ATP was measured by the mtAT 1.03 probe. j Monocytes were treated with or without β-glucan and lactate (1 mM) for 12 hrs, then acetyl-CoA, citrate, and malate levels were measured. k Monocytes were cultured in MM containing ¹³C-lactate (1 mM), indicating unlabeled glucose concentration, and treated with β-glucan (5 μg/ml) for 4 hrs, followed by mass spectrometry analyzes. Data in (a–f and h–k) are expressed as means ± SEMs, n = 3 mice per condition, two-way ANOVA. See also Supplementary Figs. 3.