IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-16877-3.html
   My bibliography  Save this article

Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis

Author

Listed:
  • Neharika Jain

    (International Centre for Genetic Engineering and Biotechnology)

  • Haroon Kalam

    (International Centre for Genetic Engineering and Biotechnology)

  • Lakshyaveer Singh

    (International Centre for Genetic Engineering and Biotechnology)

  • Vartika Sharma

    (International Centre for Genetic Engineering and Biotechnology)

  • Saurabh Kedia

    (All India Institute of Medical Sciences)

  • Prasenjit Das

    (All India Institute of Medical Sciences)

  • Vineet Ahuja

    (All India Institute of Medical Sciences)

  • Dhiraj Kumar

    (International Centre for Genetic Engineering and Biotechnology)

Abstract

Anti-tuberculosis (TB) drugs, while being highly potent in vitro, require prolonged treatment to control Mycobacterium tuberculosis (Mtb) infections in vivo. We report here that mesenchymal stem cells (MSCs) shelter Mtb to help tolerate anti-TB drugs. MSCs readily take up Mtb and allow unabated mycobacterial growth despite having a functional innate pathway of phagosome maturation. Unlike macrophage-resident ones, MSC-resident Mtb tolerates anti-TB drugs remarkably well, a phenomenon requiring proteins ABCC1, ABCG2 and vacuolar-type H+ATPases. Additionally, the classic pro-inflammatory cytokines IFNγ and TNFα aid mycobacterial growth within MSCs. Mechanistically, evading drugs and inflammatory cytokines by MSC-resident Mtb is dependent on elevated PGE2 signaling, which we verify in vivo analyzing sorted CD45−Sca1+CD73+-MSCs from lungs of infected mice. Moreover, MSCs are observed in and around human tuberculosis granulomas, harboring Mtb bacilli. We therefore propose, targeting the unique immune-privileged niche, provided by MSCs to Mtb, can have a major impact on tuberculosis prevention and cure.

Suggested Citation

  • Neharika Jain & Haroon Kalam & Lakshyaveer Singh & Vartika Sharma & Saurabh Kedia & Prasenjit Das & Vineet Ahuja & Dhiraj Kumar, 2020. "Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16877-3
    DOI: 10.1038/s41467-020-16877-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-16877-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-16877-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16877-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.