TB: Hide and seek

A Nyishi tribesman undergoing a health check-up at a medical camp organised by the Indian Army in the remote district of Arunachal Pradesh, a 2008 picture.

Even after months of treatment, tuberculosis is known to recur, leading to suffering and death. The intriguing question is where the TB bacteria hide in the body during treatment. According to a study conducted in north-eastern India, particularly Arunachal Pradesh, where the incidence of TB is much higher than in the rest of India, the dormant Mycobacterium tuberculosis hides in bone marrow stem cells to escape drug treatment. This finding, published in the latest issue of Science Translational Medicine, may help efforts to develop better therapy to target the dormant TB bacteria. Conjecturing that TB bacteria perhaps escaped the host immune defence and drug treatment by hiding inside bone marrow stem cells, Bikul Das, a stem cells researcher at Stanford University, California, and his team, along with researchers from the Forsyth Institute, Cambridge, Massachusetts, successfully recovered viable bacteria inside the CD271+ stem cells using a mouse model of TB. A clinical study was then performed in the Arunachal Pradesh/Bhutan area.

In collaboration with Research Institute of World’s Ancient Traditions, Cultures & Heritage, Roing, Arunachal Pradesh, a team of local doctors and medical professionals from the Gauhati Medical College, Das set up a temporary research lab in Roing and isolated the CD271+ stem cells from the Idu-Mishmi people suffering from this dreaded disease who participated in the study. The subjects were those who had TB and had successfully completed drug treatment. The study found evidence of dormant TB bacteria in those stem cells, which supported the finding in the U.S. animal study. The findings indicate that the dormant TB bacteria hijack a stem cell type known as mesenchymal stem cells (MSCs), which are known to migrate to the area of inflammation, including the lungs. The bacteria hide inside the CD271-expressing MSCs, and these infected MSCs reside in the bone marrow niche, which has low oxygen, so drugs and immune cells cannot reach them. This, the researchers say, could be why it is so difficult to eradicate TB from human hosts.