Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies of...

Tuberculosis remains one of the leading causes of death from a single infectious pathogen worldwide, despite the availability of antituberculosis chemotherapy and Bacillus Calmette-Guérin vaccination. Tuberculosis pathogenesis is driven by a dynamic and prolonged interplay between host protective immunity and the immune evasion strategies of Mycobacterium tuberculosis (M. tuberculosis). During infection, bidirectional host-M. tuberculosis interactions, together with immunometabolic and epigenetic reprogramming, shape granuloma formation and organization, fibrotic encapsulation, liquefactive necrosis, and ultimately determine disease progression and transmission. However, a systematic framework linking host protective immunity, M. tuberculosis immune evasion, and granuloma evolution across distinct stages of infection remains incomplete. In this review, we summarize the host-M. tuberculosis interactions that shape early innate immune recruitment, adaptive immune activation, granuloma formation and remodeling, persistent infection, granuloma breakdown, and progression to active tuberculosis. We further integrate emerging concepts of metabolic reprogramming, epigenetic reprogramming, trained immunity, tissue-resident immunity, and myeloid-derived immunosuppressive networks. Finally, we discuss how these mechanistic insights may inform the design of next-generation tuberculosis vaccines and adjunctive therapies. This review establishes a comprehensive conceptual framework for understanding tuberculosis immunopathogenesis and provides guidance for the development of antituberculosis vaccines and therapeutic strategies.