Role of Toll-like receptors in COVID-19 pathogenesis

Abstract

Introduction. This review summarizes the available information on the role of Toll-like receptors (TLRs) in the pathogenesis of the novel coronavirus infection COVID-19 induced by SARS-CoV-2. The exact pathogenesis of COVID-19 and the role of each component of innate and adaptive immunity are still unknown. Aim. Discussion of the possible role of TLRs in the immune response in COVID-19 infection. Results. Analysis of the literature in the PubMed database showed that the mechanism of penetration of SARS-CoV-2 and lysis of type II alveolocytes is the binding of the spike S-glycoprotein or capsid protein M of the virus to the receptor-binding domain of ACE2 on the surface of epithelial cells. Migration and infiltration of inflammatory cells leads to overactivation of TLR4 on the surface of alveolocytes and bronchial epithelium, shifting the process to MyD88-dependent acute inflammatory signaling and hypersecretion of proinflammatory cytokines that cause a “cytokine storm” and the development of severe complications of COVID-19 infection, in particular, acute respiratory infections, respiratory distress syndrome, pathology of internal organs, and, in some cases, the death of the patient. Conclusion. It is possible to suggest that TLRs have an impact on the immune response in COVID19 infection. Both antagonists and agonists of TLRs, depending on their type, can be examined to determine the therapeutic and negative effects of COVID-19 infection. Further research is needed to investigate TLRs and pathways for activating cytokine expression, as they indicate a direct relationship with mortality and virus susceptibility. Bioinformatic research can also help to better understand the interaction of TLRs with proteins and RNA of the SARS-CoV-2.