The Role Of Programmed Death Receptor-1 In Peripheral Immune Evasion Of Japanese Encephalitis Virus

Japanese encephalitis(JE) is a zoonosis caused by Japanese encephalitis virus(JEV) infection. As a neurotropic virus, JEV can evade the body’s immune clearance, cross the blood brain barrier and enter the CNS. Then JEV can infect nerve cells and activate microglia and astrocytes to release large amounts of inflammatory factors, leading to inflammation and tissue damage. How JEV escape from immune surveillance still remain unclear. Our previous results on JEV infected C57BL/6 mice showed the frequency of CD4~+ T cells was reduced while the expression of CD4~+ T cell surface inhibitory molecule PD-1 was significantly increased.Based on these observations, we further investigated the role of PD-1 in JEV-induced immune response with JEV-infected PD-1-/- mice, the JEV-P3 infection model was established in PD-1-/- mice, then analyzed the frequency of related immune cells and immune molecules after JEV infection. The results showed that the frequency of CD4~+ T cells increased in the early stage of JEV infection in PD-1-/- mice, which reversed the decrease of CD4~+ T cells in BALB/c mice; 3 days after JEV-P3 infection, the expression of CD274 on DC were dramatically increased in JEV-infected PD-1-/-mice compared with BALB/c mice; the duration secretion of IL-10 on MDSCs and CD19~+ B cell were extended in PD-1-/- mice; but the mortality showed no significant difference between PD-1-/- mice and BALB/c mice after JEV-P3 infection.Taken together, the increased frequency of CD4~+ T cells illustrates that the lack of PD-1 can better activate the immune response, but the increased population of the DC surface molecule CD274 and the prolonged secretion of IL-10 demonstrate that the lack of PD-1 may enhance other immunosuppressive pathway, so that JEV still can escape from peripheral immune surveillance eventually enter into the CNS and causing disease. That’s why there were no difference of mortality between PD-1-/- mice and BALB/c mice. This study contribute to a better understanding of JEV immune escape mechanism during infection and provides reference for related research.