Macrophages and dendritic cells (DCs) are key players in innate immunity, responding to pathogens through pattern recognition receptors (PRRs). Activation of these cells by pro-inflammatory stimuli, such as lipopolysaccharide (LPS), leads to a metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, similar to the Warburg effect in tumors. This metabolic reprogramming is crucial for biosynthesis, energy production, and signaling processes. The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays a central role in this switch, promoting glycolysis and inflammatory gene expression. Key mechanisms include the inhibition of mitochondrial respiration by nitric oxide (NO), increased activity of the mTOR-HIF-1α pathway, and the regulation of glycolytic enzymes like u-PFK2. Citrate and succinate also contribute to metabolic changes, with succinate stabilizing HIF-1α and promoting inflammation. M2 macrophages, alternatively activated, exhibit a different metabolic profile, relying more on OXPHOS and anti-inflammatory cytokines. Metabolic differences between M1 and M2 macrophages are central to their distinct functions in immune responses. Understanding these metabolic changes provides insights into innate immunity and potential therapeutic targets for diseases involving inflammation and immune dysfunction.Macrophages and dendritic cells (DCs) are key players in innate immunity, responding to pathogens through pattern recognition receptors (PRRs). Activation of these cells by pro-inflammatory stimuli, such as lipopolysaccharide (LPS), leads to a metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, similar to the Warburg effect in tumors. This metabolic reprogramming is crucial for biosynthesis, energy production, and signaling processes. The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays a central role in this switch, promoting glycolysis and inflammatory gene expression. Key mechanisms include the inhibition of mitochondrial respiration by nitric oxide (NO), increased activity of the mTOR-HIF-1α pathway, and the regulation of glycolytic enzymes like u-PFK2. Citrate and succinate also contribute to metabolic changes, with succinate stabilizing HIF-1α and promoting inflammation. M2 macrophages, alternatively activated, exhibit a different metabolic profile, relying more on OXPHOS and anti-inflammatory cytokines. Metabolic differences between M1 and M2 macrophages are central to their distinct functions in immune responses. Understanding these metabolic changes provides insights into innate immunity and potential therapeutic targets for diseases involving inflammation and immune dysfunction.