TLR2/NF-кB signaling may control the expansion and function of regulatory T-cells in patients with severe fever with thrombocytopenia syndrome (SFTS)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality (12-30%) that is caused by a novel bunyaviru. The mechanism by which SFTS bunyavirus (SFTSV) causes severe illness remains unclear. To evaluate the role of the TLR2 receptor pathway in regulating Treg function in the progression of SFTS disease and possible mechanisms, 29 patients with SFTS (15 mild, 14 severe) had sequential serum samples taken. The phenotypic and functional characteristics of TLR2 expression on CD4 T-cells, CD8 T-cells, and Tregs in circulation were analyzed via flow cytometry. Correlations between the frequencies of the cells mentioned above and the SFTS index (SFTSI) were evaluated in all patients with SFTS upon admission. Compared with that in healthy controls, the expression of TLR2 on CD4 T-cells and Tregs in SFTS patients was significantly increased, and the expression of TLR2 on Tregs was positively correlated with the expression of Ki-67 in Tregs and the severity of disease. Additionally, compared with those in healthy controls, the expression levels of NF-κB in Tregs were significantly increased. Collectively, SFTSV infection may induce the activation and expansion of Tregs via the activation of the TLR2/NF-кB pathway.