Alcohol induces intrahepatic humoral immunity-related suppression and delays the clearance of HBV infection.

• Alcohol increases intrahepatic B-lineage cells-related apoptosis and immunosuppressive cytokines productions. • Alcohol decreases the frequencies of intrahepatic follicular helper CD4+T cells(Tfh cells) and peripheral helper CD4+T cells(Tph cells) among CD4+T cells. • The frequrncy of Tph cells is negatively correlated to B-lineage cells related apoptosis and immunosuppressive cytokines productions. • Alcohol reduces the germinal center B cells area and the production of IL-21 by intrasplenic cells. • Alcohol delays the clearance of HBsAg, increases the level of HBeAg, and reduces the production of Hepatitis B surface antibody at 40 dpi. Alcohol consumption is widespread. As the main organ of alcohol metabolism, the liver also has an immune tolerance function. However, little is known about how alcohol affects intrahepatic immune dysregulation and hepatitis B virus (HBV) infection. In a mice model, alcohol intake increased Fas expression on intrahepatic B220+B cells and intrahepatic CD138+B cells, increased TGF-β and IL-10 production by intrahepatic CD19+B cells, and decreased frequencies of intrahepatic T peripheral helper (Tph) cells and intrahepatic T follicular helper (Tfh) cells. Tph cells, but not Tfh cells, were negatively correlated with the B-lineage cell-related apoptosis and the production of immunosuppressive cytokines. Besides, alcohol intake significantly reduced the production of IL-21 by Tfh-like cells and CD8+PD-1+ cells and reduced the area of the splenic germinal center B cells. After 4 weeks of alcohol intake, we induced HBV infection in mice by injecting plasmid pAAV-HBV1.2. Alcohol intake increased serum hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen levels, delayed HBsAg clearance and decreased anti-HBsAg antibodies production at 40 days post-injection. In conclusion, our study reveals that alcohol intake can suppress humoral immunity and impede HBV clearance, providing further evidence for alcohol abstinence in patients with HBV infection. [ABSTRACT FROM AUTHOR]