Decreased expression of toll like receptor signaling molecules in chronic HBV infected patients

Momeni, Mohammad; Zainodini, Nahid; Bidaki, Reza; Hassanshahi, Gholamhossein; Daneshvar, Hamid; Khaleghinia, Mehdi; Ebrahim, Maryam; Karimi-Googheri, Masoud; Askari, Alireza; Arababadi, Mohammad Kazemi; Kennedy, Derek

doi:10.1016/j.humimm.2013.09.015

Cited by 33 publications

(32 citation statements)

References 19 publications

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“…Further, the over-expression of MyD88 which is the universal adaptor for all TLRs with the except for TLR3 induced antiviral response and inhibited HBV replication in HepG2 and Huh7 cells [18]. In addition, the expressions of TLR7 [19], TLR9 [19,20] and signaling molecules (IRAK1, IRAK4, TRAF3 and IRF7) [21] were significantly decreased in PBMC of chronic HBV infected subjects compared with control. These findings indicate that TLRs and its induced responses play important roles in the progress of HBV infection.…”

Section: Discussionmentioning

confidence: 97%

Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of Hepatitis B Virus

Tian

Sun

Wang

et al. 2015

Cell Physiol Biochem

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Background: Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission, but most of the infants born to HBV-positive mothers are protected from infection. However, the mechanisms by which intrauterine transmission is avoided remain elusive, and the roles of toll-like receptors (TLRs) have been proposed. The aims of this study were to clarify if TLR 7 and 8 are involved in the prevention of intrauterine transmission of HBV. Methods: Real time polymerase-chain reaction (PCR) was used to determine the expression of TLRs and cytokines in placenta and trophoblasts. The expression of MyD88 was interfered with small interfering RNA (siRNA) in trophoblasts. An in intro model mimicking trophoblast barrier was established to evaluate the effect of MyD88 siRNA on HBV transmission across trophoblast barrier. Results: There were significant differences in placental expression of TLR7 (F=3.263, P=0.048) and TLR8 (F=3.257, P=0.048) among control (HBV-negative women), non-infected group (HBV-positive women whose infants were not infected) and infected group (HBV-positive women whose infants were infected). The expression of TLR7 was significantly higher in non-infected group than infected group (P=0.039) and control (P=0.043). There was a significant difference in TLR8 expression between non-infected group and control (P=0.014), and the difference was close to but not significant (P=0.074) between non-infected and infected groups. Exposure of trophoblast to HBV significantly induced the expression of TLR7 (P<0.001), TLR8 (P=0.005), MyD88 (P=0.004), interferon (IFN)-α (P=0.004), IFN-β (P<0.001) and interleukin (IL)-8 (P=0.001). When MyD88 was interfered by siRNA, the expression of IFN-α (P<0.001), IFN-β (P=0.01) and IL-8 (P<0.001) was significantly decreased while the amount of HBV transcytosed across trophoblastic barrier significantly increased (P=0.03). Conclusions: TLR7 and TLR8 on trophoblastic cells play an important role in the prevention of intrauterine HBV transmission by inhibiting HBV translocation across trophoblast.

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Section: Discussionmentioning

confidence: 97%

Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of Hepatitis B Virus

Tian

Sun

Wang

et al. 2015

Cell Physiol Biochem

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“…Two recent studies showed decreased expression of TLR signaling molecules, such as MyD88, IRAK1 and IRAK4, in PBMCs from CHB patients compared with healthy controls. 41,42 One study showed increased IL-12 and decreased IL-6 levels in the serum of CHB patients compared with that of healthy controls. However, it was not clear whether there is a correlation between the inflammatory cytokines and expression of TLR signaling molecules.…”

Section: Interaction Between Tlrs and Hbvmentioning

confidence: 99%

“…However, it was not clear whether there is a correlation between the inflammatory cytokines and expression of TLR signaling molecules. 42 During chronic HCV infection, TLR2 upregulation in peripheral blood monocytes and liver tissue was correlated with increased levels of serum TNF-a and hepatic inflammation. 43,44 These results supported the hypothesis that the changed inflammatory environment may lead to reduced expression or function of individual TLRs in CHB patients.…”

Section: Interaction Between Tlrs and Hbvmentioning

confidence: 99%

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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“…HBV surface antigen (HBsAg) in viral infected cells inhibited TLR9-dependent expression of IRF7 and nuclear translocation (28). Downregulation of IRF7 gene in HBV infected patients was indicated earlier (29). HBV infection also led to reduced IFN-α production, which is the target gene in IRF7 signaling pathway (30).…”

Section: Introductionmentioning

confidence: 99%

“…No relationship was observed between IRF7 and any human or animal models of transplantation yet, but the cross-talk between IRF7 and HBV infection was reported in a few studies (29,30). In a research focused on the expression levels of TLR signaling molecules such as IRF7, IRAK1, IRAK4, and TRAF3 in chronic HBV infected patients, results indicated that IRF7 gene was downregulated (29).…”

mentioning

confidence: 99%

Study the Cross-talk Between Hepatitis B Virus Infection and Interferon Regulatory Factors in Liver Transplant Patients

et al. 2017

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Background: Interferon regulatory factors (IRFs) as immunoregulatory molecules have a determinative antiviral role in liver transplantation outcomes and graft rejection. Hepatitis B virus (HBV) and its antigen derivatives also choose some strategies to escape from innate immune responses. Objectives: The current study aimed at evaluating inflammatory cross-talks between pattern recognition receptors (PRRs) signaling components such as IRF3 and IRF7 with HBV infection in mRNA levels in patients undergoing liver transplantation. Methods: The 46 HBV infected liver recipients were divided into rejection experienced (20) and not experienced (26) groups and a healthy control group was also considered. Peripheral mononuclear cells (PBMCs) were isolated form each studied patient on the days 1, 4, and 7 in post-transplant period. After RNA extraction and cDNA synthesis from each collected sample, the expression levels of IRF3 and IRF7 genes were evaluated using in-house SYBER Green based the real-time polymerase chain reaction (PCR) protocols. Results: The overexpression of mRNA levels of IRF3 (3.37 folds) and IRF7 (1.74 folds) on the day 1 were found in patients experiencing rejection, compared with non-rejected ones, based on initial ischemia/reperfusion (I/R) injuries. But, the mRNA levels of IRF3 (0.53 folds) and IRF7 (0.74 folds) on the day 4 were downregulated in patients with rejected transplantation, compared with non-rejected ones. Finally, reducing the expression of IRF3 (0.54 fold) on the day 7 and upregulation of IRF7 (2.38 fold) on the day 7 were found in rejected liver recipients, compared with non-rejected ones in post-transplant period. Conclusions: Downregulation of IRF3 expression in patients with HBV infection, who experienced rejection episodes in the first week post-liver transplantation indicated that they may be at higher risk for acute rejection; the hypothesis, which should be investigated in further studies.

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Decreased expression of toll like receptor signaling molecules in chronic HBV infected patients

Cited by 33 publications

References 19 publications

Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of Hepatitis B Virus

Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of Hepatitis B Virus

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

Study the Cross-talk Between Hepatitis B Virus Infection and Interferon Regulatory Factors in Liver Transplant Patients

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