HBsAg Inhibits IFN-α Production in Plasmacytoid Dendritic Cells through TNF-α and IL-10 Induction in Monocytes

Type I Interferon (IFN) is one of the first lines of defense against viral infection. Plasmacytoid dendritic cells (pDCs) are professional IFN-alpha-producing cells that play an important role in the antiviral immune response. Previous studies have reported that IFN-alpha production is impaired in chronic hepatitis B (CHB) patients. However, the mechanisms underlying the impairment in IFN-alpha production are not fully understood. Here, we report that plasma-derived hepatitis B surface antigen (HBsAg) and HBsAg expressed in CHO cells can significantly inhibit toll like receptor (TLR) 9-mediated Interferon-alpha (IFN-alpha) production in peripheral blood mononuclear cells (PBMCs) from healthy donors. Further analysis indicated that monocytes participate in the inhibitory effect of HBsAg on pDCs through the secretion of TNF-alpha and IL-10. Furthermore, TLR9 expression on pDCs was down-regulated by TNF-alpha, IL-10 and HBsAg treatment. This down-regulation may partially explain the inhibition of IFN-alpha production in pDCs. In conclusion, we determined that HBsAg inhibited the production of IFN-alpha by pDCs through the induction of monocytes that secreted TNF-alpha and IL-10 and through the down-regulation of TLR9 expression on pDCs. These data may aid in the development of effective antiviral treatments and lead to the immune control of the viral infections.