Pathogenesis of Mycobacterium tuberculosis: Intracellular dynamics

Tuberculosis remains one of the leading causes of death from a single infectious agent worldwide, despite decades of research and intervention efforts. The remarkable success of Mycobacterium tuberculosis as a human pathogen stems from its ability to survive and replicate within host macrophages, cells designed to eliminate invading microorganisms. This ability is a product of evolution. This review examines the intracellular dynamics between M. tuberculosis and host macrophages, focusing on the molecular mechanisms that underlie the capacity of M. tuberculosis to circumvent host defence systems. We explored the initial stages of infection, including attachment and phagocytosis, followed by a detailed analysis of how M. tuberculosis modifies phagosome maturation, neutralizes reactive oxygen and nitrogen intermediates, and manipulates host cell death pathways. Special attention is given to specific bacterial cell envelope components and secreted proteins that serve as critical virulence factors by modulating host immune responses, and the influence of host genetic polymorphisms on tuberculosis susceptibility and progression. Understanding these complex host-pathogen interactions provides crucial insights for developing novel therapeutic strategies targeting the intracellular phase of tuberculosis, potentially addressing the challenges of drug resistance and persistent infection.