Pathogenesis of Mycobacterium tuberculosis: Granuloma Formation and Dynamics (a review)

Tuberculosis remains one of the leading causes of mortality and morbidity worldwide, yet active disease develops in only 5-10% of infected individuals. This review explores the pathogenesis of Mycobacterium tuberculosis with a specific focus on granuloma formation and dynamics. Granulomas, the hallmark of pulmonary tuberculosis, have traditionally been viewed as host-beneficial structures that contain the pathogen. However, emerging evidence suggests a paradigm shift wherein M. tuberculosis actively manipulates granuloma formation and function to facilitate its survival and transmission. The review examines the structural organization of granulomas, the complex interplay of cytokines and immune cells involved in their formation and maintenance, and the mechanisms through which M. tuberculosis subverts host defences within this environment. Particular attention is given to the roles of foamy macrophages, caseous necrosis, and the ESX-1 secretion system in granuloma dynamics. Understanding the dual role of granulomas, both host defence mechanisms and pathogen-exploited niches, provides critical insights for developing improved therapeutic strategies against tuberculosis. Special emphasis is placed on the roles of foamy macrophages, caseous necrosis, and the ESX-1 secretion system in shaping granuloma behavior. Recognizing the granuloma’s dual function- a defense mechanism for the host and a niche exploited by the pathogen- offers valuable insights for advancing more effective tuberculosis treatments.