ArticleThe Journal of clinical investigation2020
Mycobacterium tuberculosis programs mesenchymal stem cells to establish dormancy and persistence.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 57 citations in OpenAlex.
- Doxycycline host-directed therapy in human pulmonary tuberculosis.The Journal of clinical investigation · 2021Trial
- Host-pathogen interactions in tuberculosis: from immunological mechanisms to translational applications.Cell insight · 2026Review
- Current research progress on extracellular vesicles derived from mesenchymal stem cells in tuberculosis treatment (Review).Molecular medicine reports · 2026Review
- Ly6GeLife · 2026Article
- Transcriptomic insights intoThe veterinary quarterly · 2025Article
- Global proteomics reveals pathways of mesenchymal stem cells altered by Mycobacterium tuberculosis.Scientific reports · 2024Article
- Ajoene: a natural compound with enhanced antimycobacterial and antibiofilm properties mediated by efflux pump modulation and ROS generation against M. Smegmatis.Archives of microbiology · 2024Article
- Revisiting the role of mesenchymal stem cells in tuberculosis and other infectious diseases.Cellular & molecular immunology · 2023Review
- The antidepressant sertraline provides a novel host directed therapy module for augmenting TB therapy.eLife · 2023Article
- Dormancy: There and Back Again.Molecular biology · 2022Article
- Tuberculosis: The success tale of less explored dormantFrontiers in cellular and infection microbiology · 2022Review
- Advances in adjunct therapy against tuberculosis: Deciphering the emerging role of phytochemicals.MedComm · 2021Review
- Carbohydrate Metabolism Affects Macrophage-Mediated Killing of Enterococcus faecalis.mSystems · 2021Article
- Bartonella henselae Persistence within Mesenchymal Stromal Cells Enhances Endothelial Cell Activation and Infectibility That Amplifies the Angiogenic Process.Infection and immunity · 2021Article
- Heterogeneous Host-Pathogen Encounters Coordinate Antibiotic Resilience in Mycobacterium tuberculosis.Trends in microbiology · 2021Review
- Observational
- Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection.BMC immunology · 2021Article
- Repurposing Immunomodulatory Drugs to Combat Tuberculosis.Frontiers in immunology · 2021Review
- Mesenchymal Stem Cells and Tuberculosis: Clinical Challenges and Opportunities.Frontiers in immunology · 2021Review
- Regulatory Mechanisms of Autophagy-Targeted Antimicrobial Therapeutics Against Mycobacterial Infection.Frontiers in cellular and infection microbiology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberculosis (TB) remains a major infectious disease worldwide. TB treatment displays a biphasic bacterial clearance, in which the majority of bacteria clear within the first month of treatment, but residual bacteria remain nonresponsive to treatment and eventually may become resistant. Here, we have shown that Mycobacterium tuberculosis was taken up by mesenchymal stem cells (MSCs), where it established dormancy and became highly nonresponsive to isoniazid, a major constituent of directly observed treatment short course (DOTS). Dormant M. tuberculosis induced quiescence in MSCs and promoted their long-term survival. Unlike macrophages, where M. tuberculosis resides in early-phagosomal compartments, in MSCs the majority of bacilli were found in the cytosol, where they promoted rapid lipid synthesis, hiding within lipid droplets. Inhibition of lipid synthesis prevented dormancy and sensitized the organisms to isoniazid. Thus, we have established that M. tuberculosis gains dormancy in MSCs, which serve as a long-term natural reservoir of dormant M. tuberculosis. Interestingly, in the murine model of TB, induction of autophagy eliminated M. tuberculosis from MSCs, and consequently, the addition of rapamycin to an isoniazid treatment regimen successfully attained sterile clearance and prevented disease reactivation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.