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A chronic murine model of pulmonary infection was used to assay the therapeutic efficacy of nintedanib. Macrophage transcriptome deep sequencing, a confocal assay, siRNA knockdown, Western blotting, quantitative RT\u2013PCR and a cfu assay were used to investigate the antibacterial mechanism of nintedanib.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The MIC90 of nintedanib against M. tuberculosis standard strain H37Rv was 23.56\u201340.51\u2005mg\/L. TB murine model studies showed that nintedanib, coadministered with isoniazid, rifampicin and pyrazinamide, shortened treatment duration, and ameliorated pulmonary inflammation and fibrosis. In mechanism studies, transcriptome sequencing analysis revealed that nintedanib may eliminate M. tuberculosis through up-regulating macrophage autophagy. Furthermore, inhibition of autophagy by using siRNA targeting ATG5 or the autophagy inhibitor 3-methyladenine almost completely abolished nintedanib-mediated suppression of M. tuberculosis. Nintedanib induced autophagy by the JAK2\/STAT3\/Beclin1 pathway. When JAK2 or Beclin1 were knocked down through siRNA, nintedanib no longer inhibited M. tuberculosis. JAK2 activator coumermycin A1 and STAT3 agonist colivelin also reversed this phenotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In vitro activity of nintedanib against drug-susceptible and -resistant M. tuberculosis and efficacy in murine infections warrant the continued clinical evaluation of nintedanib as a new adjuvant therapy for standard treatment of TB.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae429","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T19:23:22Z","timestamp":1733858602000},"page":"452-464","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy of nintedanib as a host-directed therapy candidate in the treatment of tuberculosis"],"prefix":"10.1093","volume":"80","author":[{"given":"Xinda","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Beijing Chest 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