{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:10:05Z","timestamp":1792613405241,"version":"4.5.0"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"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                    Interferon-gamma (IFN-\u03b3) is a key stimulator of macrophage defense against\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) and\n                    <jats:italic>Mycobacterium leprae (M. leprae)<\/jats:italic>\n                    . Both pathogens adopt measures to circumvent the effects of the immune system, weakening the impact of IFN-\u03b3 and enabling them to survive in the cells. This review synthesizes how IFN-\u03b3 overdose transacts the JAK\/STAT1-IRF1-transmitter to encourage maturation of phagolysosomes, reactive oxygen and nitrogen product generation, LC3-associated phagocytosis (LAP), autophagy, and improved antigen presentation and juxtaposes these pathways in tuberculosis and leprosy. We also explain the mechanisms by which mycobacteria counter this axis, including receptor downregulation, induction of IL-10\/SOCS, type I INF antagonism, and the impact of miRNA. Additionally, we assessed the translational application, emphasizing its benefits, potential risks, and sources of variability. Additionally, we discuss biomarker strategies related to IFN-\u03b3 activity, such as gene signatures associated with HIF-1 and active IFN-\u03b3 measurements, which could aid in selecting patients and tracking their treatment progress. The results show that macrophage-related processes are important for the treatment and diagnosis of TB and leprosy when they occur simultaneously. This highlights the need for safe and effective treatments that focus on the host and balance the protective and harmful effects of IFN-\u03b3.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2025.1679691","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T06:33:20Z","timestamp":1762842800000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["IFN-\u03b3-Driven macrophage responses in the immunity to Mycobacterium tuberculosis and Mycobacterium leprae"],"prefix":"10.3389","volume":"15","author":[{"given":"Mohd","family":"Imran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed S.","family":"Alshrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abida","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah R.","family":"Alzahrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/srep27632","article-title":"Mycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages","volume":"6","author":"Batista-Silva","year":"2016","journal-title":"Sci. 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