Toll-like receptor (TLR)-mediated innate immune responses in the control of hepatitis B virus (HBV) infection

The role of adaptive immune responses in the control of hepatitis B virus (HBV) infection is well accepted. The contribution of innate immune responses to the viral control is recognized but yet not fully understood. Toll-like receptors (TLRs) sense pathogen-associated molecule patterns and activate antiviral mechanisms including the intracellular antiviral pathways and the production of antiviral effectors like interferons (IFNs) and pro-inflammatory cytokines. Activation of the TLR3 pathway and the production of IFN-β represent one of the major mechanisms leading to the suppression of HBV replication in the liver, as shown in different in vitro and in vivo models. TLR4 signaling and TLR2 signaling result in the activation of intracellular pathways including MAPK and PI-3 K/Akt in hepatocytes and reduce HBV replication in an IFN-independent manner. HBV is able to counteract the actions of TLR3 and TLR2/4 through downregulation of TLR expression and attenuation of the cellular signaling pathways. Thus, TLR ligands are promising candidates as immunomodulators and therapeutics for the treatment of chronic HBV infection. Specific antiviral treatment against HBV could recover the TLR functions in chronic HBV infection and increase the effectiveness of therapeutic approaches based on TLR activation.