Immunopathology in human tuberculosis

Mycobacterium tuberculosis (M.tb) is a bacterial pathogen that has evolved in humans, and its interactions with the host are complex and best studied in humans. Myriad immune pathways are involved in infection control, granuloma formation, and progression to tuberculosis (TB) disease. Inflammatory cells, such as macrophages, neutrophils, conventional and unconventional T cells, B cells, NK cells, and innate lymphoid cells, interact via cytokines, cell-cell communication, and eicosanoid signaling to contain or eliminate infection but can alternatively mediate pathological changes required for pathogen transmission. Clinical manifestations include pulmonary and extrapulmonary TB, as well as post-TB lung disease. Risk factors for TB progression, in turn, largely relate to immune status and, apart from traditional chemotherapy, interventions primarily target immune mechanisms, highlighting the critical role of immunopathology in TB. Maintaining a balance between effector mechanisms to achieve protective immunity and avoid detrimental inflammation is central to the immunopathogenesis of TB. Many research gaps remain and deserve prioritization to improve our understanding of human TB immunopathogenesis.