Culturing primary mouse liver parenchymal, endothelial, or Kupffer cells with HBV antigens, hepatitis B virion, or supernatant from HBV-infected cells abrogated TLR3 and TLR4 activation and subsequently inhibited the release of IFN-β and interferon regulatory factor-3 (IRF-3) proinflammatory cytokines in an NF-kB and ERK1/2-dependent manner. Here, IRF3 is linked to hepatitis B virus infection.