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PNAS 107 (50): 21653-21658

Copyright © 2010 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / IMMUNOLOGY

Mycobacterium tuberculosis evades host immunity by recruiting mesenchymal stem cells

Shilpa Raghuvanshia, Pawan Sharmaa, Sarman Singhb, Luc Van Kaerc, and Gobardhan Dasa,1

aImmunology Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India; bDivision of Clinical Microbiology, Department of Laboratory Medicine, All India Institute of Medical Science, New Delhi 110029, India; and cDepartment of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232

Edited* by Michael B. Brenner, Harvard Medical School, Boston, MA, and approved November 5, 2010 (received for review June 7, 2010)

Abstract: Tuberculosis (TB) is the cause of 2 million deaths each year, which is the second highest cause of mortality from a single infectious disease worldwide. Resistance of these organisms to drugs has emerged as an important health concern. Alternative approaches to the prevention and treatment of tuberculosis are therefore urgently needed. Despite the generation of robust host immune responses, Mycobacterium tuberculosis (M. tb) successfully evades host immunity and establishes a persistent infection. The mechanism(s) by which M. tuberculosis manages to persist in the face of potent host immune responses remain(s) incompletely understood. Here, we demonstrate that M. tb suppresses T-lymphocyte responses by recruiting mesenchymal stem cells (MSCs) to the site of infection. We found that MSCs infiltrated tissues in mice containing M. tb organisms and T lymphocytes. We further demonstrate that MSCs suppressed T-cell responses by producing nitric oxide. Our findings reveal a key role of MSCs in the capacity of M. tb to evade host immune responses and identify these cells as unique targets for therapeutic intervention in tuberculosis.

Key Words: immunosuppression • immune tolerance


Author contributions: G.D. designed research; S.R. performed research and made all figures; P.S., S.S., and L.V.K. contributed new reagents/analytic tools; S.R. and G.D. analyzed data; and G.D. and L.V.K. wrote the paper.

The authors declare no conflict of interest.

*This Direct Submission article had a prearranged editor.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1007967107/-/DCSupplemental.

1To whom correspondence should be addressed. E-mail: dasgo{at}icgeb.res.in.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
CD271+ Bone Marrow Mesenchymal Stem Cells May Provide a Niche for Dormant Mycobacterium tuberculosis.
B. Das, S. S. Kashino, I. Pulu, D. Kalita, V. Swami, H. Yeger, D. W. Felsher, and A. Campos-Neto (2013)
Science Translational Medicine 5, 170ra13
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