The activation of macrophages and dendritic cells (DCs) by pro-inflammatory stimuli triggers a metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, similar to the Warburg effect observed in tumors. This metabolic reprogramming is facilitated by the transcription factor hypoxia-inducible factor-1α (HIF-1α), which plays a crucial role under both hypoxic and normoxic conditions. The withdrawal of citrate from the tricarboxylic acid (TCA) cycle is critical for lipid biosynthesis in macrophages and DCs, and interference with this process abolishes the ability of DCs to activate T cells. Succinate, another TCA cycle intermediate, activates HIF-1α and promotes inflammatory gene expression. These findings provide deeper insights into the role of metabolic reprogramming in innate immunity. Key mechanisms include the activation of mTOR, which increases HIF-1α expression and promotes glycolysis, and the inhibition of AMPK, which opposes the metabolic switch towards glycolysis. Additionally, the citrate carrier Slc25a1 is upregulated in macrophages and DCs, leading to increased citrate transport and metabolism, which is essential for ATP production and biosynthesis. The metabolic differences between M1 and M2 macrophages, characterized by their distinct metabolic profiles and inflammatory phenotypes, further highlight the complexity of metabolic reprogramming in innate immunity.The activation of macrophages and dendritic cells (DCs) by pro-inflammatory stimuli triggers a metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, similar to the Warburg effect observed in tumors. This metabolic reprogramming is facilitated by the transcription factor hypoxia-inducible factor-1α (HIF-1α), which plays a crucial role under both hypoxic and normoxic conditions. The withdrawal of citrate from the tricarboxylic acid (TCA) cycle is critical for lipid biosynthesis in macrophages and DCs, and interference with this process abolishes the ability of DCs to activate T cells. Succinate, another TCA cycle intermediate, activates HIF-1α and promotes inflammatory gene expression. These findings provide deeper insights into the role of metabolic reprogramming in innate immunity. Key mechanisms include the activation of mTOR, which increases HIF-1α expression and promotes glycolysis, and the inhibition of AMPK, which opposes the metabolic switch towards glycolysis. Additionally, the citrate carrier Slc25a1 is upregulated in macrophages and DCs, leading to increased citrate transport and metabolism, which is essential for ATP production and biosynthesis. The metabolic differences between M1 and M2 macrophages, characterized by their distinct metabolic profiles and inflammatory phenotypes, further highlight the complexity of metabolic reprogramming in innate immunity.