Host-Pathogen Interactions in Mycobacterium tuberculosis: From Phagosome Arrest to Granuloma Dynamics- A review

Abstract

Mycobacterium tuberculosis (Mtb) remains one of the leading causes of death from a single infectious agent despite effective antimicrobial therapy. Its success is largely attributed to its ability to survive within host macrophages, evade immune clearance, establish latent infection, and develop phenotypic drug tolerance, complicating disease control and treatment. Although these mechanisms have been widely studied, their interrelationship remains incompletely understood. This mini narrative review examines five key aspects of Mtb pathogenesis: macrophage survival, inhibition of phagosome–lysosome fusion, granuloma formation, latent versus active tuberculosis, and drug tolerance. A literature search was conducted using PubMed, Web of Science, Google Scholar, and Scopus with relevant keywords and Boolean operators. Articles published predominantly between 2016 and 2026 were included. The findings indicate that Mtb manipulates macrophage antimicrobial functions, inhibits phagosome maturation and lysosomal fusion, promotes granuloma formation that both restricts and protects bacilli, transitions between latent and active disease in response to host and environmental factors, and develops drug-tolerant persister populations that contribute to prolonged treatment and relapse. Together, these interconnected mechanisms enable long-term bacterial persistence and immune evasion. Understanding these dynamic host–pathogen interactions is essential for developing integrated diagnostic, therapeutic, and host-directed strategies to improve tuberculosis control.