Previously, it has been shown that toll-like receptor (TLR) signalling is impaired by HBsAg Belnacasan cost leading to an attenuation of innate and adaptive immune responses which may possibly facilitate chronicity of infection. Here, we aimed to analyze immune activation in HBV transgenic mice lacking the HBs antigen (1.4 tgHBV-s-mut). Methods: Liver tissue of 1.4 tgHBV-s-mut mice, HBV negative littermates, TLR3-/- and TLR3-/-/1.4 tgHBV-s-mut animals was investigated. HBxAg-targeting siRNAs or ligand for TLR3 (poly I:C) were injected intravenously. Quantitative RT-PCR, Southern blot, ELISA and western blot were performed to detect levels of immune genes,

HBV DNA, HBeAg or HBcAg. Results: Hepadnaviral replication-dependent expression of interferon beta (IFN-p), interferon sensitive selleck chemical gene 15 (ISG15), interferon-induced protein with tetratricopeptide repeats 1 (IFI-T1) was observed in 1.4 tgHBV-s-mut mice. This immune response could be normalized by treatment with HBx-Ag-targeting siRNAs and was completely abrogated in TLR3-/-/1.4 tgHBV-s-mut animals. Suppression of these TLR3-mediated immune responses led to increased HBV replication. Non-pa-renchymal liver cells were identified as source of these antiviral

responses. Further application of TLR3 ligand poly I:C significantly induced the expression of ISG15, IFI-T1, IFN-p and suppressed HBV replication in vivo and in vitro. However, the fold induction of these immune genes was significantly lowered in 1.4 tgHBV-s-mut mice compared to control animals, reflecting a HBs-independent immune evasion. Conclusions: In contrast to data from HBV-infected patients, hepatic TLR signalling was not totally

abrogated 上海皓元 in HBV transgenic mice that lack HBsAg. In 1.4 tgHBV-s-mut mice viral replication induced TLR3-mediated antiviral responses in non-parenchymal liver cells. We therefore hypothesize that HBsAg is a major component of HBV that attenuates TLR signaling thus leading to impairment of innate and adaptive immune responses in the liver. Disclosures: Hans-Peter Vornlocher – Management Position: Axolabs GmbH The following people have nothing to disclose: Catherine I. Real, Mengji Lu, Markus Hossbach, Kerstin Jahn-Hofmann, Ludger M. Ickenstein, Matthias J. John, Reinhold Schirmbeck, Melanie Lutterbeck, Kathrin Gibbert, Ulf Dittmer, Guido Gerken, Joerg F. Schlaak, Ruth Broering Background and Aim: Natural Killer (NK) cells play important roles in innate immune response in viral infection. The activation of NK cells are controlled by various activating and inhibitory NK cell receptors and many NK cell receptors have been identified. In this study, we focused on NKp46, an activating receptor, and NKG2A, an inhibitory receptor, and investigated the frequencies and function of NKp46 and NKG2A expressing NK cells in chronic hepatitis B (CHB) patients. Methods: Sixty six CHB patients and 32 healthy subjects (HS) were enrolled in this study.