Microbial agents as triggers of developing multiple sclerosis

Abstract

Multiple sclerosis (MS) currently represents a pressing medical and social issue. This is due to the high prevalence of this pathology among neurological diseases preferentially affecting young people and subsequent rapid disability. This disease still remains a mystery for medicine due to its ambiguous etiology, polymorphism of clinical manifestations and unstable course. Despite the marked development of modern instrumental diagnostic methods, pathognomonic signs have not yet been identified for multiple sclerosis allowing to diagnose the disease with high accuracy at early stages. At the moment, we may only say with confidence that MS is a neurodegenerative disease accompanied by rapid demyelination and death of nerve cells. Complex and diverse pathogenetic mechanisms suggest a multifactorial nature of the disease, which develops due to combination of external factors and hereditary predisposition, which causes altered immune tolerance. The polygenic theory of MS is most substantiated, which implies that the genotype of MS patients consists of many genes, each of which contributes to the disease development. More than 100 genes associated with MS have been identified, among which a special place is taken by the HLA system (human leukocyte antigen), which controls the interaction of immunocompetent cells and carries out an immune response. In addition, new candidate genes have been identified that contribute to the development of MS: interleukin 2 and 7 receptors (IL-2R, IL-7R), differentiation cluster 6 (CD6) and 58 (CD58), tumor necrosis factor α, interferon regulatory factor 8 (IRF8), interleukin 12А (IL-12A) and others. However, to uncover genetic predisposition, it is necessary to experience external trigger factors. The activation of demyelinating process is quite often initiated by various infectious agents, among which the most studied are Epstein–Barr virus, John Cunningham virus, acute encephalomyelitis virus, and human endogenous retroviruses. Intestinal microbiota altered by Candida albicans, Staphylococcus aureus, Acinetobacter calcoaceticus, Bacteroides, Proteobacteria and Firmicutes deserved special attention in developing neurodegenerative disorders. Such an imbalance profoundly affects immune and nervous system functioning, taking part in neurogenesis, myelination, activation of cellular and humoral immune responses. Here we review and analyze the latest data accumulated in Russian and foreign literature regarding the study of the MS epidemiological features, as well as microbiological risk factors for disease development.