Metabolic reprogramming and macrophage polarization in granuloma formation.

This review article delves into the complexities of granuloma formation, focusing on the metabolic reprogramming within these immune structures, especially in tuberculosis and sarcoidosis. It underscores the role of the monocyte-macrophage lineage in granuloma formation and maintenance, emphasizing the adaptability of these cells to environmental cues and inflammatory stimuli. Key to the discussion is the macrophage polarization influenced by various cytokines, with a detailed exploration of the metabolic shifts towards glycolysis under hypoxic conditions and the utilization of the pentose phosphate pathway (PPP) for crucial biosynthetic processes. Significant attention is given to the metabolism of L-arginine in macrophages and its impact on immune response and granuloma function. The review also highlights the role of mechanistic target of rapamycin (mTOR) signaling in macrophage differentiation and its implications in granulomatous diseases. Discoveries such as elevated PPP activity in granuloma-associated macrophages and the protective role of NADPH against oxidative stress offer novel insights into granuloma biology. The review concludes by suggesting potential therapeutic targets within these metabolic pathways to modulate granuloma formation and function, proposing new treatment avenues for conditions characterized by chronic inflammation and granuloma formation. This work contributes significantly to the understanding of immune regulation and chronic inflammation, presenting avenues for future research and therapy in granulomatous diseases.