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Front. Immunol. | doi: 10.3389/fimmu.2018.02921

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

 Biao Zhang1, Yu Liu1,  Xu Wang2,  Jieliang Li2, Xiqiu Xu1,  Le Guo1 and  WENZHE HO1, 2*
  • 1Wuhan University School of Basic Medical Sciences, China
  • 2Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, United States

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 indubced 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.

Keywords: Hepatic Stellate Cells, Hepatitis B virus, interferon-β, Interferon-λ, Toll-Like Receptor 3, Interferon-stimulated genes

Received: 08 Jun 2018; Accepted: 28 Nov 2018.

Edited by:

Aurelio Cafaro, Istituto Superiore di Sanità (ISS), Italy

Reviewed by:

Paul U. Cameron, The University of Melbourne, Australia
Antonio Bertoletti, Duke-NUS Medical School, Singapore  

Copyright: © 2018 Zhang, Liu, Wang, Li, Xu, Guo and HO. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. WENZHE HO, Wuhan University School of Basic Medical Sciences, Wuhan, China, wenzheho@temple.edu