Possible goal for new Tuberculosis-vaccine identified
A new study published in the research journal PLOS Pathogens, shows for the first time the essential role of the molecule SOCS3 in the control of Tuberculosis. This could have impact on the future development of a vaccine.
Tuberculosis is sometimes perceived as a feared killer of the past but is still a dreadful disease of mankind. One third of the world population is infected with the bacteria Mycobacterium tuberculosis that causes the disease. However, Tuberculosis is manifested only in approximately 10 percent of those infected. Still, about 2 million Tuberculosis patients die every year worldwide.
Mycobacterium tuberculosis multiplies inside white blood cells known as macrophages. In infected people who don't develop the Tuberculosis, the immune system either the bacteria or impairs bacterial multiplication. The exact mechanisms behind this are not known in detail, hampering the development of effective vaccines and treatments of the disease. Why the disease is manifested in some individual, but not in others, is not completely understood.
The recent study shows that a molecule called SOCS3 is required for control of the infection. The discovery was done using an experimental infection of mice genetically modified so that they do not express SOCS3 in different immune cells. These mice were dramatically susceptible to the infection with Mycobacterium tuberculosis.
"Like a soldier with two guns the molecule SOCS3 engages in different ways in the combat against Mycobacterium tuberculosis. We were stunned by the fact that the same molecule independently controls diverse mechanisms in different cell types," says Martin Rottenberg, Professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.
The control of Tuberculosis is hampered by the appearance of antibiotic-resistant strains. Moreover, the Tuberculosis vaccine, developed almost 100 years ago, shows low efficiency against the most common pulmonary disease. An improved understanding of how our immune responses control the infection might be used for the design of new vaccines.
"We speculate that SOCS3 could be a new target for vaccines to improve the protection against Tuberculosis," says Martin Rottenberg.
First study author is Berit Carow, postdoc at the Department of Microbiology, Tumor and Cell Biology. The study has been supported financially by EU, Vetenskapsrådet and Karolinska Institutet.
Critical and independent role for SOCS3 in either myeloid or T cells in resistance to Mycobacterium tuberculosis.
Carow B, Reuschl A, Gavier-Widén D, Jenkins B, Ernst M, Yoshimura A, et al
PLoS Pathog. 2013 ;9(7):e1003442