期刊
JOURNAL OF HEPATOLOGY
卷 63, 期 5, 页码 1077-1085出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2015.06.022
关键词
Pathogen recognition receptor; Toll-like receptor; Hepatocyte; Hepatitis B virus; Antiviral activity
资金
- ANRS (French national agency for research on AIDS and viral hepatitis)
- ANRS (CSS4)
- FINOVI (Foundation for innovation in infectiology)
- FRM (Foundation for medical research) [DEQ20110421327]
- Hoffmann-La-Roche Ltd (Switzerland division)
- INSERM
- DEVweCAN LABEX of the Universite de Lyon'', within the program Investissements d'Avenir'' [ANR-10-LABX-0061, ANR-11-IDEX-0007]
Background & Aims: HepaRG cells are considered as the best surrogate model to primary human hepatocyte (PHH) culture to investigate host-pathogen interactions. Yet their innate immune functions remain unknown. In this study, we explored the expression and functionality of Toll-like (TLR) and retinoic acid-inducible gene-1 (RIG-I)-like receptors (RLR) in these cells. Methods: Gene and protein expression levels of TLR-1 to 9 and RLR in HepaRG were mainly compared to PHH, by RT-qPCR, FACS, and Western blotting. Their functionality was assessed, by measuring the induction of toll/rig-like themselves and several target innate gene expressions, as well as the secretion of IL-6, IP-10, and type I interferon (IFN), upon agonist stimulation. Their functionality was also shown by measuring the antiviral activity of some TLR/RLR agonists against hepatitis B virus (HBV) infection. Results: The basal gene and protein expression profile of TLR/RLR in HepaRG cells was similar to PHH. Most receptors, except for TLR-7 and 9, were expressed as proteins and functionally active as shown by the induction of some innate genes, as well as by the secretion of IL-6 and IP-10, upon agonist stimulation. The highest levels of IL-6 and IP-10 secretion were obtained by TLR-2 and TLR-3 agonist stimulation respectively. The highest preventive anti-HBV activity was obtained following TLR-2, TLR-4 or RIG-I/MDA-5 stimulations, which correlated with their high capacity to produce both cytokines. Conclusions: Our results indicate that HepaRG cells express a similar pattern of functional TLR/RLR as compared to PHH, thus qualifying HepaRG cells as a surrogate model to study pathogen interactions within a hepatocyte innate system. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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