{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:17:54Z","timestamp":1793312274739,"version":"4.5.0"},"reference-count":135,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"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 (TB) is still a major global health threat, worsened by the advancement of multidrug-resistant and extensively drug-resistant strains of\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ). Autophagy is a natural degradation and immune process that plays a critical role in the defence against intracellular pathogens, including\n                    <jats:italic>Mtb<\/jats:italic>\n                    . However,\n                    <jats:italic>Mtb<\/jats:italic>\n                    has developed complex mechanisms to evade autophagy by modulating phagosome-lysosome fusion, inhibiting xenophagy, and modifying host signaling pathways, including mTORC1 and AMPK, thereby suppressing epigenetically autophagy-related genes. These immune evasion strategies identify autophagy as a highly attractive target for host-directed therapies (HDTs). In many experimental models, several pharmacological and repurposed compounds, such as mTOR inhibitors, AMPK activators, lysosomal modulators, peptides, and small-molecule inhibitors, are promising factors in restoring autophagy, promoting bacterial clearance, and ameliorating inflammation. Despite the bright prospects of these preclinical studies, the intricacies of cellular pathways, the lack of selective autophagy modulators, the limited biomarkers, and the still inadequate models for translational research remain problematic. In this review, we summarise current insights into\n                    <jats:italic>Mtb<\/jats:italic>\n                    -mediated disruption of autophagy, evaluate emerging autophagy-enhancing HDTs, and highlight key biological and translational gaps. Further development of selective, system-level autophagy modulators may offer powerful adjunct therapies to improve TB treatment outcomes, especially in the era of escalating drug resistance.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1896798","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:57:32Z","timestamp":1787579852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Autophagy in tuberculosis: advances, translational gaps, and the promise of host-directed therapies"],"prefix":"10.3389","volume":"16","author":[{"given":"Manjunath","family":"Challa","sequence":"first","affiliation":[{"name":"Department of Bacteriology, National Institute for Research in Tuberculosis \u2013 ICMR","place":["Chennai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessy","family":"Padma B","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, National Institute for Research in Tuberculosis \u2013 ICMR","place":["Chennai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivakumar","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, National Institute for Research in Tuberculosis \u2013 ICMR","place":["Chennai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4289","DOI":"10.4049\/jimmunol.0803736","article-title":"Vitamin d-directed rheostatic regulation of monocyte antibacterial responses","volume":"182","author":"Adams","year":"2009","journal-title":"J.\u00a0Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"522","DOI":"10.3390\/medicina57060522","article-title":"Autophagy induction as a host-directed therapeutic strategy against Mycobacterium tuberculosis infection","volume":"57","author":"Adikesavalu","year":"2021","journal-title":"Medicina"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.tube.2016.03.010","article-title":"Effect of 1,25-dihydroxyvitamin D3 on the expression of mannose receptor, DC-SIGN and autophagy genes in pulmonary tuberculosis","volume":"99","author":"Afsal","year":"2016","journal-title":"Tuberculosis (Edinb)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"361","DOI":"10.4161\/auto.5.3.7662","article-title":"Autophagy induction by trehalose counteracts cellular prion infection","volume":"5","author":"Aguib","year":"2009","journal-title":"Autophagy"},{"key":"B5","doi-asserted-by":"publisher","first-page":"821","DOI":"10.3390\/idr13030074","article-title":"Review of the effectiveness of various adjuvant therapies in treating Mycobacterium tuberculosis","volume":"13","author":"Amin","year":"2021","journal-title":"Infect. 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