The HBV-induced microenvironment impairs the antiviral immune response triggered by TLR9 stimulation in human peripheral immune cells

Abstract

Hepatitis B virus (HBV) causes acute liver inflammation and leads chronic hepatitis, accountingfor approximately 1 million deaths from hepatocellular carcinoma and cirrhosis annually.Worldwide, more than 350 million people infected with HBV require a life-long treatment withHBV polymerase inhibitors as the immunotherapy with pegylated interferon α (PEG-IFNα) iseffective in a very limited number of patientsIFNα serves as a crucial mediator of the earlyantiviral response. IFNα secretion can be induced by multiple pattern recognition receptor(PRR) pathways including the toll-like receptor 9 (TLR9) activation. TLR9 is expressed in Blymphocytes and plasmacytoid dendritic cells (pDC). pDCs secrete large amounts of IFNα inresponse to TLR9 activation. TLR9 response is negatively regulated by micro-RNA miRNA-146a,which inhibits the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), akey protein of the TLR9 pathway.