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Abstract
Title | Hepatitis B virus surface antigen suppresses Innate and adaptive immune responses of murine and human liver cells | Speaker: | Ruth Bröring | Author: | M. Jiang1, M. Trippler1, R. Broering1*, L. Poggenpohl1, G. Gerken1, M. Lu2, J.F. Schlaak1 | Affiliation: | 1Department of Gastroenterology and Hepatology, University Hospital of Essen, 2Institute of Virology, University Hospital of Essen, Essen, Germany. *[email protected] | Background and aims: It has recently been shown that Toll-like receptor (TLR) signaling in murine non-parenchymal (NPC) liver cells is suppressed in the presence of Hepatitis B surface antigen (HBsAg). It is not clear, however, whether this is also relevant for adaptive and human immune responses and how this effect is mediated.
Methods: Peripheral blood mononuclear cells (PBMCs) from chronic HBV infected patients were stimulated by TLR3 ligands in the absence or presence of autologous serum. Murine Kupffer cells (KC), sinusoidal endothelial cells (LSEC) and hepatocytes as well as human LSEC and hepatocytes were stimulated with TLR3 ligand Poly I:C in the presence or absence of HBsAg. Expression of cytokines and TLR3 was analyzed by quantitative rt-PCR. Mixed lymphocyte reactions (MLR) were performed to study T cell activation induced by TLR-stimulated NPC. Activation of transcription factors was assessed by western blot and reporter gene assays.
Results: TLR3-induced production of IFN-γ was suppressed in PBMC from patients with high HBsAg-levels (p< 0.0006) compared to PBMC isolated from patients with low HBsAg-levels. In the presence of autologous serum, TLR3 induced IFN-γ production was inhibited in case of HBV-containing serum. Activation of T lymphocytes which was induced by TLR3-activated NPC was potently suppressed by HBsAg. This suppressive effect was associated with enhanced IL-10 production that could be reverted by IL-10 antibodies. While Poly I:C-induced TLR3 expression remained unchanged, TLR-induced activation of NFκB, IRF-3 and MAPKs was potently suppressed by HBsAg.
Conclusions: These findings may, at least in part, explain how HBV evades innate and adaptive immune responses to establish a persistent infection. |
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