Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection
Tuberculosis (TB) treatment regimens are lengthy, causing non-adherence to treatment. 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2021-10-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/14/10/dmm049018 |
| _version_ | 1819099057077878784 |
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| author | Kamlesh Bhatt Madhuri Bhagavathula Sheetal Verma Graham S. Timmins Vojo P. Deretic Jerrold J. Ellner Padmini Salgame |
| author_facet | Kamlesh Bhatt Madhuri Bhagavathula Sheetal Verma Graham S. Timmins Vojo P. Deretic Jerrold J. Ellner Padmini Salgame |
| author_sort | Kamlesh Bhatt |
| collection | DOAJ |
| description | Tuberculosis (TB) treatment regimens are lengthy, causing non-adherence to treatment. 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. |
| first_indexed | 2024-12-22T00:40:49Z |
| format | Article |
| id | doaj.art-6d65048b44aa4deea31ae57be740ec92 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-22T00:40:49Z |
| publishDate | 2021-10-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-6d65048b44aa4deea31ae57be740ec922022-12-21T18:44:41ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112021-10-01141010.1242/dmm.049018049018Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infectionKamlesh Bhatt0Madhuri Bhagavathula1Sheetal Verma2Graham S. Timmins3Vojo P. Deretic4Jerrold J. Ellner5Padmini Salgame6 Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM 87131, USA Autophagy Inflammation and Metabolism (AIM) Center of Biomedical Research Excellence University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA Tuberculosis (TB) treatment regimens are lengthy, causing non-adherence to treatment. 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.http://dmm.biologists.org/content/14/10/dmm049018tuberculosishost-directed therapyrapamycininflammation |
| spellingShingle | Kamlesh Bhatt Madhuri Bhagavathula Sheetal Verma Graham S. Timmins Vojo P. Deretic Jerrold J. Ellner Padmini Salgame Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection Disease Models & Mechanisms tuberculosis host-directed therapy rapamycin inflammation |
| title | Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection |
| title_full | Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection |
| title_fullStr | Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection |
| title_full_unstemmed | Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection |
| title_short | Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection |
| title_sort | rapamycin modulates pulmonary pathology in a murine model of mycobacterium tuberculosis infection |
| topic | tuberculosis host-directed therapy rapamycin inflammation |
| url | http://dmm.biologists.org/content/14/10/dmm049018 |
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