Publication Details
Abstract
Mycobacterium tuberculosis (PTB) is a significant health problem in the world, which is linked with intricate immuno-histopathological alterations in the lung parenchyma. Granuloma formation is the characteristic of PTB, a highly structured immune structure of infected macrophages, epithelioid cells, multinucleated giant cells, lymphocytes, and fibroblasts. This review discusses the cellular crosstalk and tissue remodeling mechanisms which form the basis of disease progression and pulmonary damage. After inhalation, M. tuberculosis is phagocytosed by alveolar macrophages, which activates the innate immune pathway via pattern recognition receptors and release of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interferon-γ. These intermediates ensure the recruitment and activation of T helper 1 (Th1) cells, cytotoxic T lymphocytes, and other monocytes, strengthening the integrity of granuloma, as well as trying to control the multiplication of bacteria. Nevertheless, chronic immune stimulation facilitates overproduction of matrix metalloproteinase (MMP) and extracellular matrix destruction, as well as the interference with alveolar architecture. Fibrosis is caused by fibroblast proliferation and collagen deposition, whereas necrotizing granulomas and caseation are caused by dysregulated apoptosis and hypoxic stress by macrophages respectively. Macrophage crosstalk with both neutrophils and T cells increases oxidative stress, cytokine signaling, which mediate protective immune response and collateral tissue damage. Clinical outcomes related to the dissemination of host defense and immunopathology, including latent infection to cavitary disease depend on balance. The knowledge of the molecular networks controlling immune cell communication and structural remodeling in PTB could be used to help design host-directed therapies which can restrain tissue destruction and maintain antimicrobial activity.