TLR3 Activation of Hepatic Stellate Cell Line Suppresses HBV Replication in HepG2 Cells

• Published in: Frontiers in immunology 2018-12, Vol.9, p.2921-2921
• Main Authors: Zhang, Biao, Liu, Yu, Wang, Xu, Li, Jieliang, Xu, Xiqiu, Guo, Le, Ho, Wen-Zhe
• Format: Article
• Language: English
• Subjects: Culture Media - pharmacology; Hep G2 Cells; hepatic stellate cells; Hepatic Stellate Cells - immunology; Hepatic Stellate Cells - metabolism; Hepatitis B - immunology; Hepatitis B - virology; hepatitis B virus; Hepatitis B virus - immunology; Humans; Immunity, Innate; Immunology; interferon-stimulated genes; interferon-β; interferon-λ; Interferons - immunology; Interferons - metabolism; Liver - cytology; Liver - immunology; Liver - virology; Phosphorylation - immunology; Poly I-C - genetics; Receptors, Interferon - immunology; Receptors, Interferon - metabolism; STAT Transcription Factors - immunology; STAT Transcription Factors - metabolism; Toll-like receptor 3; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 3 - metabolism; Virus Replication - drug effects; Virus Replication - immunology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.02921

There is limited information about the role of hepatic stellate cells (HSCs) in the liver innate immunity against hepatitis B virus (HBV) infection. We thus examined whether hepatic stellate cell line (LX-2) can be immunologically activated and produce antiviral factors that inhibit HBV replication in HepG2 cells. We found that LX-2 cells expressed the functional Toll-like receptor 3 (TLR3), activation of which by PolyI:C resulted in the selective induction of interferon-β (IFN-β) and IFN-λs, the phosphorylation of IFN regulatory factor 3 (IRF3) and IRF7. When HepG2 cells were treated with supernatant (SN) from PolyI:C-activated LX-2 cells, HBV replication was significantly inhibited. IFN-β and IFN-λ appeared to contribute to LX-2 SN-mediated HBV inhibition, as the antibodies to IFN-β and IFN-λ receptors could largely block the LX-2 SN action. Mechanistically, LX-2 SN treatment of the HepG2 cells induced a number of antiviral IFN-stimulated genes (ISGs: ISG20, ISG54, ISG56, OAS-1, Trim22, and Trim25) and facilitated the phosphorylation of STATs. These observations support further studies on the role of HSCs in the liver innate immunity against HBV infection.