Indian scientists have discovered cells that harbour within themselves immunity from tubercle bacilli. Is mesenchymal stem cells, which many not only in fat but also in other connective tissues. The researchers found that mycobacteria are able to multiply within these cells and acquire resistance to drugs, and anti-inflammatory properties of stem cells only increase this effect. This may explain the lack of effectiveness of TB vaccines and drugs. Work published in the journal Nature Communications.
TB infection continues to be a major threat, despite the existence of vaccines and drugs. Probably the fact that vaccines are not very effective and much better protection against leprosy (which causes a close relative of Mycobacterium tuberculosis) than directly from tuberculosis. Medications do not always help — and then there are strains with extensively drug-resistant.
In addition, many drugs are much better able to cope with the tuberculosis Bacillus in vitro than inside the body. Perhaps this is due to the fact that this bacterium is able to survive inside cells — primarily macrophages, which engulf her, but cannot fully digest.
A group of scientists under the leadership of Dhiraj Kumar (Dhiraj Kumar) from the International centre for genetic engineering and biotechnology in new Delhi have suggested that M. tuberculosis can hide from the immune response within human cells. Good shelter, according to the researchers, could be mesenchymal stem cells (MSCS) which are found in large numbers in the bone marrow and adipose tissue, and less in other connective tissues. On the one hand, they previously discovered the mycobacteria. On the other hand, MSK is known as a modulator of the immune system, and you can imagine that suppressing inflammation, they are playing into the hands of a tubercular stick.
For a start, the authors infected with Mycobacterium MSCS from adipose tissue and found that it is successfully able to reproduce. They then worked on the culture of cells with bacteria inside of two common anti-TB drugs: isoniazid and rifampicin. Even in maximum doses (5 µg/ml) these medicines were powerless against 5 and 15 percent, respectively, of bacteria that survived treatment.
The researchers suggested that MSCS may contribute to the drug resistance of bacteria, pumping drugs out of cells by ABC Transporter- common family of transport proteins on the cell membrane. On the surface of MSCS there are two proteins of this family — ABCC1 and ABCG2. When the authors blocked the production of both proteins by RNAi, the drugs were able to destroy almost all bacilli, leaving alive only 2-4 percent of the population.
However, under the action of blocker of ABC transporters, the total number of bacteria in the cells (though not resistant to antibiotics) increased. This led researchers to believe that MSK is still actively struggling with their colonizers, and the conveyors can be used not only for pumping drugs, but also to provide a corrosive environment in the lysosomes by which cells digest bacteria. And indeed, when MSCS was affected by rapamycin (a drug that enhances the maturation of lysosomes), mycobacteria cells was less (p = 0,0145).
Then the authors investigated how infection of tubercle bacilli is associated with anti-inflammatory properties of MSCS. It is known that these cells are able to identify a number of signaling substances, including prostaglandins. The researchers found that the concentration of prostaglandin E2 is increased almost an order of magnitude when MSCS infected with Mycobacterium leprae. Therefore, they suggested that, if to block his selection, then the MSC will stop being a safe haven. And indeed, when they infected mice with TB and treated them with celecoxib (which blocks the signal path prostaglandin E2), the number of bacteria in the MSC of their lungs decreased by two orders of magnitude.
Thus, the role of stem cells in the development of tuberculosis infection have been mixed. On the one hand, they fight bacteria, digesting them inside itself, on the other hand, is pumped from the cells of TB drugs. And suppressing inflammation in the surrounding tissue, MSCS support the viability of their colonizers. This phenomenon, the authors offer to explain the lack of effectiveness of vaccines and drugs, which could be enhanced by blocking anti-inflammatory effect of MSCS.
Earlier we talked about other ways of dealing with the causative agent of tuberculosis: use of antibiotics “custom”, genetically modified bacteriophages and even vitamin B7 (or rather, lack thereof). In addition, the researchers put forward the hypothesis that the spread of TB among people contributed to the development of the fire.