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- Title
Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis.
- Authors
Jain, Neharika; Kalam, Haroon; Singh, Lakshyaveer; Sharma, Vartika; Kedia, Saurabh; Das, Prasenjit; Ahuja, Vineet; Kumar, Dhiraj
- 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. Treatment of tuberculosis needs to be taken for several weeks, despite good potency of drugs in vitro. Here, the authors show that mesenchymal stem cells can harbor Mycobacterium tuberculosis providing a niche for evasion of anti-bacterial drugs and cytokines.
- Subjects
MESENCHYMAL stem cells; MYCOBACTERIUM tuberculosis; TUBERCULOSIS in cattle
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-16877-3