Study On The Antiviral Immune Mechanism Of Severe Fever With Thrombocytopenia Syndrome

Objective:(1)Explaining the immune response of CD8~+T cells,CD4~+T cells and NK cells in peripheral blood with fever and thrombocytopenia syndrome.(2)To investigate the effect of CD14~+CD16~+intermediate monocytes on CD8~+T cells in patients with severe fever with thrombocytopenia syndrome(SFTS).Methods:(1)Serum samples were collected from healthy subjects,SFTS patients at the onset and recovery stages The concentrations of inflammatory factors and chemokines were detected by flow cytometry microsphere array technique.(2)Mononuclear cells(PBMCs)were isolated from peripheral blood of healthy people,patients with SFTS in onset and convalescence by density gradient centrifugation.(3)Detection of phenotype and function of CD8~+T,CD4~+T cells,NK cells and monocytes by flow cytometry.(4)Peripheral blood PBMCs of SFTS patients and healthy people were obtained by density gradient centrifugation,and stimulated and cultured under appropriate conditions in vitro to detect the phenotype and function of CD8~+T cells activated in vitro.Compared with the results of flow cytometry of directly isolated peripheral blood cells,the cell response mechanism of SFTS patients was further verified.Results:(1)Inflammatory cytokines storm in patients with fever with thrombocytopenia syndrome.(2)The percentage or absolute value of multiple lymphocytes and monocytes decreased in SFTS patients.(3)CD8~+T cells were activated in peripheral blood of SFTS patients.CD8~+T cells in SFTS patients showed a stronger antiviral response and a stronger proliferative capacity than healthy controls.(4)The activation function of CD8~+T cells in SFTS patients returned to normal level after the disease progressed to recovery stage,and the antiviral ability remained high.(5)CD4~+T cells and NK cells in peripheral blood of SFTS patients were activated and the expression of ki67 was significantly increased.(6)The percentage and absolute value of CD14~+CD16~+intermediate monocytes in peripheral blood of SFTS patients increased significantly.T High expression of chemokine CXCL10 in intermediate monocytes of peripheral blood in patients with SFTS,and the ligand CXCR3 of CXCL10 was highly expressed in CD8~+T cells.CD80,CD86 and HLA-ABC molecules were highly expressed in intermediate monocytes of SFTS patients.Conclusions:During SFTSV infection,CD8~+T cells,CD4~+T cells and NK cells in the body are activated,and CD8~+T cells showed a more active phenotype and increased expression of antiviral moleculesand increased expression of antiviral molecules.Their activation level and cytokine secretion ability can be used as clinical indicators of disease recovery together with viral RNA,body temperature and platelet count of patients.CD4~+T cells play an immunosuppressive role in SFTS infection.In addition,our study reveals a potential pathway by which CD8~+T cells are rapidly activated in the host after infection with the novel Bunyavirus and are recruited by intermediate monocytes primarily via CXCL10.The results of this study may have important clinical significance for further diagnosis and treatment of novel Bunyavirus infection.