Smoking and tuberculosis
The cause of the increased risk of tuberculosis in smokers has been found
Oleg Lischuk, N+1
An international group of researchers has found out the mechanism that increases the risk of developing tuberculosis when infected with mycobacteria. This allowed scientists to explain why the risk is significantly increased in smokers. The results of the study are published in the journal Cell (Berg et al., Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration).
Getting into the body (usually through the respiratory tract), the causative agent of tuberculosis Mycobacterium tuberculosis encounters macrophages, which serve as the first line of immune defense.
A macrophage that absorbs mycobacteria. ZEISS Microscopy
These cells absorb mycobacteria and digest them with the help of lysosomes – organelles that are filled with protein-destroying enzymes. In some cases, the pathogen manages to avoid destruction, and it uses macrophages to spread and consolidate in the body. In particular, mycobacterium causes immune cells to gather in dense clusters that form characteristic tubercles-granulomas (hence the name of the disease – tuberculum in Latin means "tubercle"). Uninfected macrophages approach granulomas, trying to destroy them by digesting dead immune cells and the microbes contained in them. If this fails, mycobacteria use the dead cells of the decaying granuloma as a nutrient medium, and the living ones as a new "vehicle".
A research team led by Cambridge and Washington Universities conducted a series of experiments on infecting a model fish with a relative of the causative agent of tuberculosis Mycobacterium marinum. RNA sequencing and quantitative PCR have shown that mutant fish with a deficiency of SNAPC1B (polypeptide 1B of the small nuclear RNA activation complex) have the greatest susceptibility to mycobacteria. The result of this mutation was a significant increase in the volume of macrophage lysosomes and the deficiency of the enzyme cathepsin in them. Similar cell changes are observed in people with mutations in the SNAPC1 gene.
Performing their function of cleaning tissues from waste products and cell decay, altered macrophages are unable to fully digest them, and are gradually overloaded with overflowing lysosomes, increasing in size and losing the ability to move normally. Such cells cannot reach the granuloma with sufficient speed, which allows mycobacteria to multiply and spread.
The researchers obtained a similar effect by overloading danio-rerio macrophages with microscopic particles of high-molecular dextran labeled with a fluorescent substance. By studying macrophages obtained from smokers, former smokers and non-smokers, scientists were convinced that many cells of smokers, just as in the experiment with fish, are overloaded with lysosomes with solid combustion products and are not capable of normal migration and destruction of mycobacteria. In former smokers, the proportion of altered macrophages was significantly less. Thus, smoking, as well as genetic predisposition, dramatically increases the risk of developing tuberculosis in contact with the pathogen.
Diagram from the article in Cell – VM
"The good news is that quitting smoking reduces the risk – it allows defective macrophages to die naturally, after which they are replaced by healthy cells," concluded researcher Joe Keane.
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28.03.2016