title: HBsAg inhibits IFN-α production in plasmacytoid dendritic cells through TNF-α and IL-10 induction in monocytes.
abstract: Type I Interferon (IFN) is one of the first lines of defense against viral infection. Plasmacytoid dendritic cells (pDCs) are professional IFN-α-producing cells that play an important role in the antiviral immune response. Previous studies have reported that IFN-α production is impaired in chronic hepatitis B (CHB) patients. However, the mechanisms underlying the impairment in IFN-α 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-α (IFN-α) 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-α and IL-10. Furthermore, TLR9 expression on pDCs was down-regulated by TNF-α, IL-10 and HBsAg treatment. This down-regulation may partially explain the inhibition of IFN-α production in pDCs. In conclusion, we determined that HBsAg inhibited the production of IFN-α by pDCs through the induction of monocytes that secreted TNF-α 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.
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China.
authors.forename: Bisheng
authors.initials: B
authors.lastname: Shi
authors.forename: Guangxu
authors.initials: G
authors.lastname: Ren
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Hu
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.forename: Zhanqing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000276:immunology / Q000378:metabolism*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10