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Each year, high rates of morbidity and mortality worldwide are a consequence of chronic respiratory infections due to\n                    <jats:italic>Mycobacteria<\/jats:italic>\n                    . According to the World Health Organization (WHO), in 2023, 10.8\u2009million individuals fell ill with\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb), resulting in an estimated 1.25\u2009million deaths. This positions tuberculosis (TB) as the leading cause of death from a single pathogen worldwide after the coronavirus disease (COVID\u201019) pandemic. On the other hand, the cases of people affected by nontuberculous mycobacteria (NTM) have risen globally, but the precise incidence and prevalence of both pulmonary and extrapulmonary disease remain unknown. In Europe, nontuberculous mycobacterial pulmonary diseases affect between 0.2 and 2.9 per 100\u2009000 individuals, mainly patients with cystic fibrosis (CF) and non\u2010CF bronchiectasis. The diagnosis and treatment of mycobacterial infections are challenging and complex, frequently requiring long\u2010duration treatments with several antibiotics, which in most cases leads to poor patient outcomes. As the role of immune cells has been extensively assessed, in this Review, we summarize the current knowledge about the contribution of epithelial cells in the early steps of\n                    <jats:italic>Mycobacteria<\/jats:italic>\n                    infections. Additionally, we describe how human lung organoid technology provides new tools to better understand host\u2013\n                    <jats:italic>Mycobacteria<\/jats:italic>\n                    interactions in the airways and test new therapeutic targets.\n                  <\/jats:p>","DOI":"10.1111\/febs.70265","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T02:37:51Z","timestamp":1758508671000},"page":"1587-1611","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lung organoids as a human system for\n                    <i>Mycobacteria<\/i>\n                    infection modeling and drug testing"],"prefix":"10.1111","volume":"293","author":[{"given":"Stephen Adonai","family":"Leon\u2010Icaza","sequence":"first","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale (IPBS) Universit\u00e9 de Toulouse, CNRS, UPS  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Verg\u00e9","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale (IPBS) Universit\u00e9 de Toulouse, CNRS, UPS  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"Mazars","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale (IPBS) Universit\u00e9 de Toulouse, CNRS, UPS  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Berry","sequence":"additional","affiliation":[{"name":"Laboratory of Pathogen Host Interactions (LPHI) Universit\u00e9 Montpellier, CNRS  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6795-5448","authenticated-orcid":false,"given":"C\u00e9line","family":"Cougoule","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale (IPBS) Universit\u00e9 de Toulouse, CNRS, UPS  France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,21]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20235868"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.76"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2016.1170599"},{"key":"e_1_2_13_5_1","unstructured":"AMR(2016)Tackling drug\u2010resistant infections globally: final report and recommendations. 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