Researchers at Sechenov University and the Research Institute of Fundamental and Clinical Immunology have found that tumor necrosis factor (TNF), which plays a critical role in protecting against tuberculosis, can under certain conditions also cause tissue damage and disease progression. This was reported by the university’s press service. The findings, published in the journal Biomolecules, pave the way for more precise immunotherapies that retain TNF’s protective effects while reducing its harmful side effects.
More than 300 scientific papers on the mechanisms of action of TNF have been analyzed by the group of Russian scientists. The results revealed that TNF plays a pivotal role in inflammatory processes and is essential for the development and maintenance of granulomas. These are specialized immune structures that encapsulate sites of infection and prevent the dissemination of mycobacteria throughout the body.
Additionally, TNF activates macrophages that are responsible for engulf and destroying Mycobacterium tuberculosis. However, when TNF is produced excessively, the increased inflammatory response that is is triggered can disrupt the organized structure of granulomas, cause cell death, and contribute to lung tissue destruction.
The scientists focused on the differences between soluble and membrane-bound forms of TNF, as well as its interaction with TNFR1 and TNFR2 receptors. The authors emphasize that the outcome of the disease depends not only on the level of TNF, but also on a variety of factors. These include the type and density of receptors expressed on different cells, the stage of infection, features of macrophage metabolism, and the ratio of proinflammatory and regulatory cytokines.
The study confirmed the clinical risk that the use of tumor necrosis factor (TNF) blockers in the treatment of autoimmune diseases, such as rheumatoid arthritis, psoriasis, and Crohn’s disease, may lead to the reactivation of latent tuberculosis. This is due to the suppression of TNF’s ability to maintain granuloma structure and activate macrophages’ protective functions.
The research, conducted with the support of a grant from the Russian Science Foundation, paves the way for the development of selective therapies.
It was previously announced that Rospatent had identified several promising Russian developments in tuberculosis diagnosis and treatment. These include new vaccines, methods of diagnosis, and treatments for resistant forms of the disease. Among the developments are a multiepitope polypeptide from Sirius and a compound from the Institute Pasteur that is effective against resistant strains of MDRTB and XDRTB.