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Inadequate treatment can lead to relapse and the development of drug resistance TB. Furthermore, patients often exhibit residual lung damage even after cure, increasing the risk for relapse and development of other chronic respiratory illnesses. Host-directed therapeutics are emerging as an attractive means to augment the success of TB treatment. In this study, we used C3HeB\/FeJ mice as an experimental model to investigate the potential role of rapamycin, a mammalian target of rapamycin inhibitor, as an adjunctive therapy candidate during the treatment of Mycobacterium tuberculosis infection with moxifloxacin. We report that administration of rapamycin with or without moxifloxacin reduced infection-induced lung inflammation, and the number and size of caseating necrotic granulomas. Results from this study strengthen the potential use of rapamycin and its analogs as adjunct TB therapy, and importantly underscore the utility of the C3HeB\/FeJ mouse model as a preclinical tool for evaluating host-directed therapy candidates for the treatment of TB.<\/jats:p>","DOI":"10.1242\/dmm.049018","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T17:40:10Z","timestamp":1630950010000},"source":"Crossref","is-referenced-by-count":27,"title":["Rapamycin modulates pulmonary pathology in a murine model of <i>Mycobacterium tuberculosis<\/i> infection"],"prefix":"10.1242","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7130-7796","authenticated-orcid":false,"given":"Kamlesh","family":"Bhatt","sequence":"first","affiliation":[{"name":"Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuri","family":"Bhagavathula","sequence":"additional","affiliation":[{"name":"Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3654-9874","authenticated-orcid":false,"given":"Sheetal","family":"Verma","sequence":"additional","affiliation":[{"name":"Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham S.","family":"Timmins","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3624-5208","authenticated-orcid":false,"given":"Vojo P.","family":"Deretic","sequence":"additional","affiliation":[{"name":"Autophagy Inflammation and Metabolism (AIM) Center of Biomedical Research Excellence University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerrold J.","family":"Ellner","sequence":"additional","affiliation":[{"name":"Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2245-3767","authenticated-orcid":false,"given":"Padmini","family":"Salgame","sequence":"additional","affiliation":[{"name":"Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"2021102612395737800_DMM049018C1","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.immuni.2013.08.026","article-title":"Autophagy regulates phagocytosis by modulating the expression of scavenger receptors","volume":"39","author":"Bonilla","year":"2013","journal-title":"Immunity"},{"key":"2021102612395737800_DMM049018C2","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.ijid.2014.12.016","article-title":"Tuberculosis and chronic respiratory disease: a systematic review","volume":"32","author":"Byrne","year":"2015","journal-title":"Int. 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