TUBERCULOSIS: Cracking the secrets of the tuberculosis germ

N. Gopal Raj
A team of Indian researchers has discovered a way in which the tuberculosis bacterium is able to remain dormant for many years in the bodies of those it infects, emerging to cause disease when their immune system weakens.

The World Health Organisation estimates that one-third of the world's population is infected with Mycobacterium tuberculosis. But the vast majority of its victims do not ever become sick. In others, however, the disease can manifest after several years.
Figuring out how the microbe is able to survive in people for long periods of time, fending off their immune response, could lead to new therapies for latent infections.

Infection process
When a person with active tuberculosis coughs, sneezes, speaks or spits, the germs get spewed out. Other people get infected by inhaling some of these germs.
As the bacterium sets about establishing itself in its new and unwilling host, cells of the person's immune system rush in to kick out the interloper.
If the immune system is unsuccessful in doing so, as is often the case, a small clump of cells, known as a granuloma, forms in the course of the tussle.
The bacteria get confined to the granuloma and their spread is checked.
A team of scientists — led by Gobardhan Das of the International Centre for Genetic Engineering and Biotechnology in Delhi — has now found that a class of stem cells, known as mesenchymal stem cells (MSCs), plays a complicated role in maintaining the granulomas.
The team's work is appearing this week in the Proceedings of the National Academy of Sciences of the United States of America.

Dual role
MSCs are like the two-headed Roman god Janus, Dr. Das said when he spoke to this correspondent. On the one hand, they limit bacterial replication within the granuloma. On the other, they also inhibit the immune system's T cells, preventing them from clearing up the infection.
In the early stages, when some of the cells of the immune system's quick-response team themselves become infected by the microbe, they raise an alarm by producing signalling molecules called chemokines. The MSCs are attracted to the granuloma by these chemokines.
The MSCs surround the granuloma, positioning themselves between the infected immune cells and the T cells that target the pathogens.
In addition, the MSCs produce nitric oxide. Although nitric oxide is toxic to the bacteria, it is produced only in quantities sufficient to check their replication, not kill them.
The nitric oxide, however, also inhibits the T cell responses, Dr. Das added.
When the immune system weakens — as happens during infection with the Human Immunodeficiency Virus (HIV), which causes AIDS — this can influence the MSCs to stop producing nitric oxide.
As a result, the bacteria can begin to proliferate and the tuberculosis infection gets reactivated.
Consequently, the MSCs could be potential targets for therapeutic intervention in tuberculosis, the scientists note in the paper.
The research was an important step towards better understanding the pathology of tuberculosis, said K.N. Balaji of the Indian Institute of Science in Bangalore, who also studies the bacterium but was not involved in the work.
The tuberculosis bacterium has many immune evasion strategies.
“This happens to one of the new ones, which has not been reported earlier,” he pointed out.

http://www.thehindu.com/health/medicine-and-research/article936113.ece