Low TH17 expression associaton with chronic hepatitis B viral infection by means of reducing viral specific IFNγ releasing in a HBV infection model of IL-17 KO mice

Abstract

BACKGROUND AND AIM: Chronic hepatitis B infection (CHB) is associated with T-cell dependent viral specific immune response. As IL-17 may constitute both early initiator of T-cell inflammatory response and essential element of cytokine network that bridges the immune system to hematopoiesis, some effects on HBV were explored in both patients and IL-17 KO mice. METHODS: Forty-two CHB patients were divided into two groups according to their HBV markers, which are Group A: HBeAg+ with normal ALT and Group B: HbsAg–, anti-HBs+. IL-17A expression level was compared after incubating the peripheral blood mononuclear cells (PBMC) with HBV antigen. Viral specific IFNγ releasing cells and TH17 phenotype were analyzed by ELISpot and FACS respectively. To explore the correlation between Th17 and anti-viral immunity, HBV mice model was created in IL-17 KO mice by hydrodynamic injection (HDI) through the tail vein with PAAV-HBV plasmid. Results: After incubation with HBcAg, IL-17 mRNA expression, Th17 and IFNγ frequencies increased significantly in Group B than in Group A (P<0.01 to 0.001). Th17/CD45RO frequency was significantly higher in Group B than in Group A. Both Th17 and IFNγ-releasing cells mostly come from memory activated T cells. In Group A, IFNγ releasing cells increased significantly and dose-dependently when the PBMCs were exposed to IL-17. IL-17 itself did not enhance PBMCs’ ability to kill AD38 and HepG2 cell lines. It has neither inhibition to HBV replication in AD38 no cytotoxicity to HepG2 growth in vitro. Three weeks after HBV-plasmid injection, HBsAg was completely clearance in wild type C57, while it was until the 3rd month after HBV HDI that all 19 IL-17 KO mice became HBsAg negative. Viral specific IFN releasing cells were much lower in IL-17 KO mice than in wild type mice during the first two weeks after HBV HDI. Anti-HBs antibody was 1000 times lower in IL-17 KO mice than in wild type mice. CONCLUSION: Anti-HBV immunity depends on Th17 as well as IL-17 expression in both CHB patients and HBV mice model at the early stage of infection. Low expression in IL-17 might be one of important factors associated with chronic HBV infection.