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Does TB Hijack Mesenchymal Stem Cells?
The microbe Mycobacterium tuberculosis (Mtb) causes the deadly disease tuberculosis (TB) in millions of humans and infects billions of others without causing apparent clinical manifestations (latent TB infection). Mtb achieves this spectacular success despite being vigorously attacked by the host immune system. Das et al. speculated that Mtb may escape the host immune response by hiding inside bone marrow stem cells. The bone marrow provides a niche where hematopoietic, mesenchymal, and endothelial stem cells reside. These cells share a common cell surface marker (CD133). When Das et al. infected human CD133+ bone marrow stem cells in vitro with Mtb, most of the bacteria infected the mesenchymal stem cell population that also expresses the cell surface marker CD271. This result suggested that CD271+ bone marrow mesenchymal stem cells (BM-MSCs) may provide a protective niche where Mtb can reside and protect itself from the host immune system. Indeed, in a well-characterized mouse model of dormant TB infection, Das et al. were able to recover viable bacteria from inside the CD271+ BM-MSCs 6 months after infection. Next, Das and colleagues recruited individuals who had taken a full drug regimen to treat their TB and who were now apparently free of infection. They recovered viable Mtb from the CD271+ BM-MSCs of some of these individuals even though the treated patients were diagnosed as TB-free. Moreover, because CD271+ BM-MSCs self renew and have molecular drug efflux pumps that prevent internalization of foreign molecules, these results have direct implications for developing new TB drugs and may explain why it is so difficult to treat latent TB.
- Copyright © 2013, American Association for the Advancement of Science
