Abstract
Tuberculosis is an infectious disease spread through airborne droplet nuclei. Mycobacterium tuberculosis is the etiological agent of this infection. Mycobacteria can cause active tuberculosis or asymptomatic latent infection due to its complex biology and host immunological responses. The genes of mycobacteria can change alveolar macrophages and boost their resistance to autophagosome-lysosome fusion. However, only 5%-10% of infected individuals progress to the active form. In this context, multiple factors are associated with the progression of the disease. Thus, the review aims to analyze the essential factors linked to the progression from latent to active tuberculosis. The mycobacterium genome closely links these factors. Importantly, mycobacteria possess numerous genes to act as a self-defense mechanism against autophagosome-lysosome fusion. The PE_PGRS proteins play an essential role in this mechanism. This protein, when combined with Rab1A, helps activate Rab1A GTP, hence boosting mTOR and preventing autophagy. The presence of certain miRNAs, probably miR-142-3p, reduced the development of the phagosome in macrophages; circRNA-0003528 helped change macrophages related to Mycobacterium by increasing CTLA4 and decreasing miR-224-5p, miR-324-5p, and miR-488-5p. Single-cell technologies like RNA sequencing can properly examine adaptive immune cell types in healthy people and patients, including CD4+, CD8+ T, and B cells. Deficiency of CD4+ T cells increases the risk of TB and can transform an infection into active tuberculosis. Therefore, research on autophagy-regulated genes and T-cell-mediated immune response, along with transcriptome analyses will determine the pathogenesis of tuberculosis, differentiate between active and latent TB, and facilitate the critical role of diagnostic biomarkers.