Role of Toll-like receptor gene polymorphism in pathogenesis of new coronavirus infection

Abstract

The review article contains data from literature which concern the role of Toll-like receptors (TLRs), immune sensors that play a key role in the systemic response to both bacterial and viral infections, e.g., in pathogenesis of a new coronavirus infection (COVID-19, SARS-CoV-2 infection). With advent of COVID-19, which has reached the scale of a pandemic, the interest in studying predictive factors for the severity of the infectious process has acquired a new cycle. The previous epidemics caused by severe acute respiratory syndrome virus (SARS-CoV), as well as the Middle East respiratory syndrome coronavirus (MERS-CoV), helped us to understand the degree of immune response in these conditions, as well as to suggest medical approaches to the pathogens of this family, i.e., which measures should be taken, and what long-term forecasts may be encountered for the SARS-CoV-2 outbreaks. Each of the 10 human TLRs recognizes a specific structure within a bacterial / viral or fungal pathogen. The effect on TLR activates the inflammatory signaling cascade via mediators, i.e., intracellular TIR domains mediated by adapter proteins. These reactions lead to the production of the most important antiviral response substances. The factors that lead to reduced / increased expression of TLR genes include gene polymorphisms which control the functioning of the immune system in some ways, thus causing a reduced, or hyperinflammatory response to an infectious agent. Genetic heterogeneity is likely to explain, at least partially, the wide range of clinical manifestations of COVID-19 infection in general population. Therefore, there is an increased interest in studies of these receptors, the degree of their expression throughout the infectious process, the polymorphisms of the TLR-encoding genes, and, consequently, the opportunity of using clinical and laboratory tests for their qualitative and quantitative assessment, as well as selection and prospects of further treatment in each personal case.