{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:40:30Z","timestamp":1777480830262,"version":"3.51.4"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Tuberculosis is an infectious disease spread through airborne droplet nuclei.\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    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%\u201310% 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\n                    <jats:italic>PE_PGRS<\/jats:italic>\n                    proteins play an essential role in this mechanism. This protein, when combined with\n                    <jats:italic>Rab1A<\/jats:italic>\n                    , helps activate\n                    <jats:italic>Rab1A<\/jats:italic>\n                    GTP, hence boosting\n                    <jats:italic>mTOR<\/jats:italic>\n                    and preventing autophagy. The presence of certain miRNAs, probably\n                    <jats:italic>miR-142-3p<\/jats:italic>\n                    , reduced the development of the phagosome in macrophages;\n                    <jats:italic>circRNA<\/jats:italic>\n                    -\n                    <jats:italic>0003528<\/jats:italic>\n                    helped change macrophages related to Mycobacterium by increasing CTLA4 and decreasing\n                    <jats:italic>miR-224-5p, miR-324-5p<\/jats:italic>\n                    , and\n                    <jats:italic>miR-488-5p<\/jats:italic>\n                    . 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.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1666138","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:43:08Z","timestamp":1769582588000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Functional analysis of distinct factors linked to the development of latent to active tuberculosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Karthikeyan","family":"Sundaram","sequence":"first","affiliation":[{"name":"Department of Herbal Pharmacology and Environmental Sustainability, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education","place":["Kelambakkam, Chennai, Tamilnadu, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkataraman","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Division of Medical Research, SRM Medical College Hospital and Research Centre","place":["Kattankulathur, Chennai, Tamilnadu, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.ijtb.2025.06.004","article-title":"The spectrum of extra pulmonary tuberculosis: Emphasizing the importance of microbiological diagnosis- A case series","author":"Aghoram","year":"2025","journal-title":"Indian J. 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