Researchers from León point to gene IL26 as a candidate for measuring tuberculosis susceptibility
Cristina G. Pedraz/DICYT Not all people infected by tuberculosis bacteria (Mycobacterium tuberculosis) fall ill. It is estimated that almost a third of the world's population is infected, but only a small percentage (some 8.6 million people) actually develop the disease. Researchers from the Internal Medicine Service of the Complejo Asistencial Universitario de León (CAULE) and the Instituto de Biomedicina (Ibiomed) of the University of León have been working for seven years on the analysis of the immune response to tuberculosis.
“Most of the population is relatively resistant to the disease and it is not well understood why few people fall ill in relative terms”, explains Octavio M. Rivero Lezcano, one of the members of the research team.
The scientific community has evidence that some groups of people are particularly susceptible to tuberculosis, such as diabetics, oncological patients, or the elderly, in which the disease appears more frequently although the reasons for this are unknown. “Our group is interested in finding out why these people are more susceptible at a cell and molecular level, as if we are capable of understanding this we will be in a position to try to strengthen their immune system against bacteria”, he adds.
Currently the main treatment against tuberculosis is antibiotic in nature, although some strains are multi-resistant or extremely resistant. They may even be totally resistant to make all known antibiotics inefficient. In this case “the prognosis of patients is very poor and the level of mortality is extremely high”, the researcher points out, emphasising that “if we are capable of understanding susceptibility perhaps we will be able to mitigate the immune deficiencies and protect people from the disease without the need for antibiotics”.
Susceptibility in the elderly
In a study recently published in the scientific journal Immunology, the research team from León has taken a closer look at tuberculosis susceptibility in the elderly. To do so it has studied macrophages (cells of the immune system that are mainly infected by bacteria) of elderly people both with tuberculosis and free from tuberculosis.
Essentially the macrophages take care of absorbing all the foreign bodies that enter the organism, such as bacteria, although in the case of tuberculosis “the bacterium is such a special one and is so well adapted to humans that it is capable of entering the macrophage and multiplying inside it to end up destroying the macrophage and spreading to others, which is how the disease develops”.
The researchers have carried out a microarray or DNA chip study (devices that allow the analysis of the differential expression of genes and monitor simultaneously the levels of thousands of them) of macrophages obtained from eight old people with tuberculosis and eight old people free from tuberculosis in cells infected in vitro, with the aim of making a comparison in the expression of genes.
“We wanted to find out how the macrophage of a tuberculosis patient reacts to the bacteria compared to the macrophage of a person free from tuberculosis. We have carried out a molecular analysis and have obtained a list of some 70 genes; they are expressed in a different way in the macrophages of an old person with tuberculosis and in those of an old person free from the disease”, Rivero Lezcano explains.
The scientific team is particularly interested in cytokines (proteins in charge of stimulating the immune system), which means that its members were especially struck by the only cytokine present in this list of differentially expressed genes, IL26. “Very little is known about this cytokine; it has scarcely been characterised and we do not understand its function well, which means that this study is one of the first to begin to allocate it a biological value”, he adds.
Also differently expressed in young people
Subsequently the researchers have extended the study to young people to check whether what they had observed was a differential factor in the elderly or whether on the contrary it was generally unrelated to age. They determined that IL26 was also differently expressed in young people with tuberculosis and young people free from tuberculosis.
Finally, by using a complete blood model the scientific group infected blood in vitro and found that in the presence of Il-26 the blood lost its capacity to eliminate the bacteria. “IL26 harms the immune response, which means that the gene is a candidate for being a biomarker for measuring tuberculosis susceptibility. Nevertheless, our studies are in their infancy and more work is needed. There is evidence that it takes part but we do not know to what extent”, he warns.
The group's next objective is therefore to study the function of IL26 in greater depth and to characterise more genes from the list obtained, in short "taking steps to understand how these genes influence tuberculosis susceptibility”.
|Guerra‐Laso, J. M., Raposo‐García, S., García‐García, S., Diez‐Tascón, C., y Rivero‐Lezcano, O. M. (2015). “Microarray analysis of Mycobacterium tuberculosis‐infected monocytes reveals IL26 as a new candidate gene for tuberculosis susceptibility”. Immunology, 144(2), 291-301.|