Coronavirus activates a stem cell-mediated defense mechanism that reactivates dormant tuberculosis: implications in COVID-19 pandemic

  1. Lekhika Pathak
  2. Sukanya Gayan
  3. Bidisha Pal
  4. Joyeeta Talukdar
  5. Seema Bhuyan
  6. Sorra Sandhya
  7. Herman Yeger
  8. Debabrat Baishya
  9. Bikul Das

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Abstract

We postulate that similar to bacteria, adult stem cells may also exhibit an innate defense mechanism to protect their niche. Here, we provide preliminary data on stem cell based innate defense against a mouse model of coronavirus, murine hepatitis virus-1 (MHV-1) infection. In a mouse model of mesenchymal stem cell (MSC) mediated Mycobacterium tuberculosis ( Mtb ) dormancy, MHV-1 infection in the lung exhibited 20 fold lower viral loads than the healthy control mice, suggesting the potential enhancement of an anti-MHV-1 defense by Mtb . This defense mechanism involves the in vivo expansion and reprogramming of CD271+MSCs in the lung to an enhanced stemness phenotype. The reprogrammed MSCs facilitate the activation of stemness genes, intracellular Mtb replication, and extracellular release of Mtb . The conditioned media of the reprogrammed MSCs exhibit direct anti-viral activity in an in vitro model of MHV-1 induced toxicity to type II alveolar epithelial cells. Thus, our data suggest that reprogrammed MSCs exert a unique innate defense against MHV-1 by activating dormant Mtb. The molecular details of this anti-viral defense mechanism against coronavirus could be further studied to develop a vaccine against COVID-19.

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  1. Version published to 10.1101/2020.05.06.077883v2 on bioRxiv
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    SciScore for 10.1101/2020.05.06.077883: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Development of stem cell mediated mice model of Mtb reactivation: All the necessary experimental procedures were undertaken in accordance with approvals of Institutional Animal Ethics Committee, Gauhati University and Institutional Ethics Committee of KaviKrishna Laboratory.
    IRB: MHV-1 infection into mice: Parental virus strain; MHV-1 was obtained from American Type Culture Collection (ATCC) and cultured inside the BSC-class II facility at KaviKrishna Laboratory in accordance with approval of “Institutional Bio-safety Committee” and “Institutional Ethics Committee” of KaviKrishna Laboratory.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe 6-8-week-old C57BL/6 female mice were obtained from National Institution of Nutrition, Hyderabad, India and were maintained in the animal house of Gauhati University at pathogen free condition as previously described (17).

    Table 2: Resources

    Antibodies
    SentencesResources
    First, mouse CD271 antibody (mouse clone ME20.4, catalog number Ab8877; Abcam, Cambridge, MA) was phycoerythrin (PE) conjugated by SiteClick antibody labeling kit (catalog numberS10467; Life Technologies, Grand Island, NY).
    CD271
    suggested: (Abcam Cat# ab8877, RRID:AB_306830)
    Experimental Models: Organisms/Strains
    SentencesResources
    In vitro cytoprotection assay against MHV-1 infection: The type II alveolar epithelial (ATII) cells of healthy C57BL/6 mice were first isolated as previously described (52) by isolating CD45−, and EPCAM+ cells using immunomagnetic sorting (53).
    C57BL/6
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistics: Statistical analysis was carried out using GraphPad Prism version 4.0 (Hearne Scientific Software, Chicago, IL, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  3. Version published to 10.1101/2020.05.06.077883v1 on bioRxiv