Poly(I:C) Induces Distinct Liver Cell Type-Specific Responses in Hepatitis B Virus-Transgenic Mice In Vitro, but Fails to Induce These Signals In Vivo

Stefan Schefczyk; Xufeng Luo; Yaojie Liang; Martin Trippler; Mengji Lu; Heiner Wedemeyer; Hartmut H Schmidt; Ruth Broering

doi:10.3390/v15051203

Poly(I:C) Induces Distinct Liver Cell Type-Specific Responses in Hepatitis B Virus-Transgenic Mice In Vitro, but Fails to Induce These Signals In Vivo

Viruses. 2023 May 19;15(5):1203. doi: 10.3390/v15051203.

Authors

Stefan Schefczyk¹, Xufeng Luo¹, Yaojie Liang¹, Martin Trippler¹, Mengji Lu², Heiner Wedemeyer^{1

3}, Hartmut H Schmidt¹, Ruth Broering¹

Affiliations

¹ Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany.
² Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
³ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.

Abstract

Immunopathology in hepatitis B virus (HBV) infection is driven by innate and adaptive immunity. Whether the hepatitis B surface antigen (HBsAg) affects hepatic antiviral signalling was investigated in HBV-transgenic mouse models that either accumulate (Alb/HBs, Tg[Alb1HBV]Bri44), lack (Tg1.4HBV-s-mut3) or secrete (Tg1.4HBV-s-rec (F1, Tg1.4HBV-s-mut × Alb/HBs) the HBsAg. Herein, the responsiveness of TLR3 and RIG-I in primary parenchymal and non-parenchymal liver cells was determined in vitro and in vivo. Cell type-specific and mouse strain-dependent interferon, cytokine and chemokine expression were observed by LEGENDplex™ and validated by quantitative PCR. In vitro, the hepatocytes, liver sinusoidal endothelial cells and Kupffer cells of Tg1.4HBV-s-rec mice showed poly(I:C) susceptibilities similar to the wild-type controls, while in the remaining leucocyte fraction the interferon, cytokine and chemokine induction was reduced. On the contrary, poly(I:C)-injected 1.4TgHBV-s-rec mice showed suppressed interferon, cytokine and chemokine levels in hepatocytes but increased levels in the leucocyte fraction. Thus, we concluded that liver cells of Tg1.4HBV-s-rec mice, which produce HBV particles and release the HBsAg, responded to exogenous TLR3/RIG-I stimuli in vitro but exhibited a tolerogenic environment in vivo.

Keywords: hepatitis B surface antigen; hepatitis B virus; immune evasion; pattern recognition; toll-like receptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines / metabolism
Endothelial Cells / metabolism
Hepatitis B Surface Antigens / genetics
Hepatitis B Surface Antigens / metabolism
Hepatitis B virus*
Hepatitis B* / metabolism
Hepatocytes
Interferons / metabolism
Liver
Mice
Mice, Transgenic
Poly I-C / metabolism
Poly I-C / pharmacology
Toll-Like Receptor 3 / genetics
Toll-Like Receptor 3 / metabolism

Substances

Hepatitis B Surface Antigens
Toll-Like Receptor 3
Interferons
Cytokines
Poly I-C

Grants and funding

R.B. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) 398762835 and 450164446. R.B. received internal funds (Programm zur internen Forschungsförderung Essen, IFORES).