Toll-like receptor-stimulated non-parenchymal liver cells can regulate hepatitis C virus replication

Broering, Ruth; Wu, Jun; Zhao, Meng; Hilgard, Philip; Lu, Mengji; Trippler, Martin; Szczeponek, A.; Gerken, Guido; Schlaak, Joerg F.

doi:10.1016/j.jhep.2008.01.028

Cited by 89 publications

(88 citation statements)

References 26 publications

(33 reference statements)

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“…Our group has reported that poly(I:C)-stimulated liver cells, including hepatocytes (4), LSECs, KCs (3,32), and hematopoietic stem cells (HSCs) (33), can directly suppress the replication of hepatotropic viruses (HBV and HCV) in a type I IFN-dependent manner. This is in accordance with data indicating that the elimination of HBV was abolished in IFN-␣␤R Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 99%

Poly(I:C) Treatment Leads to Interferon-Dependent Clearance of Hepatitis B Virus in a Hydrodynamic Injection Mouse Model

Huang

Zhao

et al. 2014

J Virol

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Section: Discussionmentioning

confidence: 99%

Poly(I:C) Treatment Leads to Interferon-Dependent Clearance of Hepatitis B Virus in a Hydrodynamic Injection Mouse Model

Huang

Zhao

et al. 2014

J Virol

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“…Abe et al [52] demonstrated that murine macrophages overexpressing NS3, NS3/4A, NS4B, or NS5A showed a strong suppression of TLR4 signaling. NS5A interacts with MyD88 to prevent IRAK-1 recruitment and cytokine production, such as IL-1, IL-6, and IFN-b response to the ligands for TLR4 [53].…”

Section: Hcv Infectionmentioning

confidence: 99%

“…Broering et al [53] found that supernatants from TLR4-stimulated non-parenchymal liver cells (Kupffer cells and sinusoidal epithelial cells) led to potent suppression of HCV replication in murine HCV replicon bearing MH1 cells through IFN-b and induction of IFN-stimulated genes. These novel findings are of particular relevance for the control of HCV replication by the innate immune system of the liver.…”

Section: Hcv Infectionmentioning

confidence: 99%

The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases

Soares¹,

et al. 2010

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Toll-like receptor 4 (TLR4) is a pattern recognition receptor that functions as lipopolysaccharide (LPS) sensor and whose activation results in the production of several pro-inflammatory, antiviral, and anti-bacterial cytokines. TLR4 is expressed in several cells of healthy liver. Despite the constant confrontation of hepatic TLR4 with gut-derived LPS, the normal liver does not show signs of inflammation due to its low expression of TLR4 and ability to modulate TLR4 signaling. Nevertheless, there is accumulating evidence that altered LPS/TLR4 signaling is a key player in the pathogenesis of many chronic liver diseases (CLD). In this review, we first describe TLR4 structure, ligands, and signaling. Later, we review liver expression of TLR4 and discuss the role of LPS/TLR4 signaling in the pathogenesis of CLD such as alcoholic liver disease, nonalcoholic fatty liver disease, chronic hepatitis C, chronic hepatitis B, primary sclerosing cholangitis, primary biliary cirrhosis, hepatic fibrosis, and hepatocarcinoma.

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“…The activation of TLR 1-9 on non-parenchymal liver cells, including KCs, leads to the production of IFN-β in mice, which inhibits the replication of HCV. 31 Studies have shown that the level of TLR3 and TLR7 in HCV-infected patients' peripheral blood are both lower than in healthy controls, and that these levels correlate with the level of IFN-α. 3 The reduction of TLRs on KCs may be closely related to immune tolerance toward and chronicity of HCV.…”

Section: Immune Tolerance Mediated By Kcs In Hbv/hcvmentioning

confidence: 99%

Kupffer cell in the immune activation and tolerance toward HBV/HCV infection

Yuan¹,

Zhang²,

et al. 2017

Adv Clin Exp Med

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Kupffer cells (KCs) are macrophages that are found in the sinusoids of the liver. KCs are a crucial part of the innate immune system, acting as scavengers and phagocytes. KCs and sinusoidal endothelial cells together form the first immune barrier of the portal system. Studies show that KCs can not only maintain homeostasis in the immune response, but also facilitate the pathogenesis of type B and type C hepatitis (HBV/HCV) through their antigen-presenting function and secretion of soluble mediators. KCs can express toll-like receptors (TLRs), Fas ligand (FasL) and programmed cell death ligand 1 (PD-L1), and secrete large amounts of inflammatory factors leading to immune tolerance toward HBV/HCV. On the one hand, KCs contribute to the clearance of HBV/HCV due to their nature as innate immune cells. At the same time, KCs induce immune tolerance toward HBV/HCV, which leads to chronicity of the infection. The dual role of KCs in the immune response toward HBV/HCV means it is a gigantic challenge for scientists to illuminate the detailed mechanisms involved, but it also offers important potential therapeutic targets.

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Toll-like receptor-stimulated non-parenchymal liver cells can regulate hepatitis C virus replication

Cited by 89 publications

References 26 publications

Poly(I:C) Treatment Leads to Interferon-Dependent Clearance of Hepatitis B Virus in a Hydrodynamic Injection Mouse Model

Poly(I:C) Treatment Leads to Interferon-Dependent Clearance of Hepatitis B Virus in a Hydrodynamic Injection Mouse Model

The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases

Kupffer cell in the immune activation and tolerance toward HBV/HCV infection

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