Reduced Toll-Like Receptor 3 Expression in Chronic Hepatitis B Patients and Its Restoration by Interferon Therapy

Huang, Yi Wen; Lin, Shih Chang; Shu, Wei; Hu, Jersan; Chang, Hsing Cheng; Huang, Shih‐Han; Chen, Ding‐Shinn; Chen, Pei‐Jer; Hsu, Ping–I; Yang, Shwu Huey; Kao, Jia‐Horng

doi:10.3851/imp2630

Cited by 46 publications

(46 citation statements)

References 37 publications

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“…However, pegylated-IFN or entecavir treatment may induce a sustained virological response that is correlated with a restoration of TLR3 and TLR9 expression. 9,81 In the WHVinfected woodchuck model, we also found that TLR2 expression in PBMCs was negatively correlated with WHV viral loads during acute WHV infection, and increased if WHV loads were suppressed in woodchucks by antiviral treatment. 12 However, these studies did not address the question of whether the functionality of TLRs was also restored by antiviral treatment.…”

Section: Using Tlr Agonists For Immunotherapy In Chronic Hbv Infectionmentioning

confidence: 62%

“…However, recent studies have suggested that antiviral treatment in chronic HBV patients can restore the expression of TLRs in PBMCs. 9,12,81 Huang et al demonstrated that chronic HBV patients had lower TLR3 and TLR9 mean fluorescence intensities on PBMCs, liver Kupffer cells and hepatocytes. Hepatic TLR3 and TLR9 mRNA were also significantly reduced in patients.…”

Section: Using Tlr Agonists For Immunotherapy In Chronic Hbv Infectionmentioning

confidence: 99%

“…Recent studies have indicated that TLR expression in peripheral immune cells, liver immune cells, and hepatocytes changed during chronic HBV infection accompanied by impaired TLR functions. [6][7][8][9] Meanwhile, TLR-mediated innate immune responses have been shown to inhibit HBV replication in hepatocytes and animal models. [10][11][12][13][14] Stimulation of innate immune responses with TLR agonists may further 1 improve the immunotherapeutic effect of combination strategies against the hepadnaviral infection.…”

Section: Introductionmentioning

confidence: 99%

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Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

Zhang

Yang

et al. 2014

Cell Mol Immunol

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It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus (HBV) infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors (TLRs) sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons (IFNs) and pro-inflammatory cytokines. Experimental results from in vitro and in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T-and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

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Section: Using Tlr Agonists For Immunotherapy In Chronic Hbv Infectionmentioning

confidence: 62%

Section: Using Tlr Agonists For Immunotherapy In Chronic Hbv Infectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

Zhang

Yang

et al. 2014

Cell Mol Immunol

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“…8 Human KCs have been proven to express TLR 2-4, while expression of TLR1-9 and retinoic-acid-inducible geneI(RIG-I) have been detected in KCs from rats and mice. 9,10 KCs also express mannose receptors and CD14. 3 The detailed mechanisms of the interaction between KC receptors and HBV/HCV viral protein still remain to be elucidated.…”

Section: Kc Receptors Activated During Hbv/hcv Infectionmentioning

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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“…After the antiviral theraby, the level of TLR3 can be promoted and almost restored. 23 HBV/HCV may influence the produce of immuneregulation cells and improve the tolerance of immune activities. In some study of mouse, it's suggested that the HCV core protein would cuase the higher product of IL-10, and IL-10 could help with immunity tolerance.…”

Section: Kcs Regulate the Immune In Hbv / Hcv Infectionmentioning

confidence: 99%

Mechanism of Kupffer cells in hepatitis infected by hepatitis B and C virus

et al. 2017

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The infection of hepatitis B virus or hepatitis C virus (HBV / HCV) is the most common cause of the chronic liver disease. Kupffer cells (KCs), the largest number of viscera macrophages, are located in the sinusoid of the hepar and play an extremely significant role in hepatic chronic inflammation after HBV / HCV infection. KCs could affect the secretion of cytokines and the interaction among cells via a variety of signalling pathways and they could regulate the inflammatory response and immune activities as well. The activation of KCs could balance inflammation and anti-inflammation, maintaining the stability of internal environment in vivo. Studies of KCs have the significance of the understanding of pathogenic mechanisms and the access to the treatment of HBV/HCV infection. Meanwhile, such studies might help to delay the development of fibrosis, cirrhosis and even carcinoma of liver after HBV / HCV infection.

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Reduced Toll-Like Receptor 3 Expression in Chronic Hepatitis B Patients and Its Restoration by Interferon Therapy

Abstract: CHB patients have reduced TLR3 expression on PBMCs, independent of age, gender and ALT, and on liver cells. Patients with pegylated-interferon-induced SVR have a more significant restoration of TLR3 expression than those under entecavir.

Cited by 46 publications

References 37 publications

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

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

Mechanism of Kupffer cells in hepatitis infected by hepatitis B and C virus

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