Raghuvanshi S, Sharma P, Singh S, Van Kaer L, Das G. Mycobacterium tuberculosis evades host immunity by recruiting mesenchymal stem cells. Proc Natl Acad Sci U S A. 2010 Dec 6. [Epub ahead of print]
On the early drug discovery front, this study may provide researchers additional areas to target for compounds against tuberculosis. Raghuvanshi, et al. conducted experiments in mice investigating the role of mesenchymal stem cells (MSCs) in infection with tuberculosis.
Granulomas caused by the recruitment of various cells (macrophages, epithelioid cells, and lymphocytes) to the site of the rapidly replicating bacteria. There is an equilibrium that develops in this granuloma between the immune response and the growth of M.tb. Overall results showed that the MSCs act both to confine the Mycobacterium tuberculosis (M. tb.) organisms within granulomas and to inhibit the response of M.tb specific T cells. Some key points from the article:
- Through observation of T cells in both infected and uninfected mice, it was confirmed that accessory cells (i.e., MSCs) contribute to the inhibition of T-cell proliferation. This observation does not seem limited to just polyclonal activation of T cells.
- MSCs seem to induce regulatory T cells to establish T-cell tolerance, a state in which a T cell can no longer respond to an antigen, thereby suppressing the activation of the immune system to M. tb.
- MSCs can be found surrounding the granuloma-like structure (mice do not get true caseous granulomas as seen in human disease) with live M.tb. found within the clusters of the MSCs.
- When in close proximity to both live M. tb. and cytokine producing T-cells, the MSCs produce nitric oxide, which is toxic to the pathogen, inhibiting bacterial replication.
- MSCs do not cause general immunosuppression, but limit the immune suppression to the area of infection within infected organs.
The authors concluded that MSCs may be potential targets for therapeutic interventions against tuberculosis.