HCV core and NS3 proteins manipulate human blood-derived dendritic cell development and promote Th 17 differentiation

Tu, Zhengkun; Hamalainen-Laanaya, Heli K.; Nishitani, Chiaki; Kuroki, Yoshio; Orloff, Mark S.

doi:10.1093/intimm/dxr104

Cited by 28 publications

(30 citation statements)

References 33 publications

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“…It has been reported that HCVc induces TLR2-mediated activation of monocytes171923, and manipulates monocyte differentiation into dendritic cells21. Thus, we next investigated whether the impaired M1 and M2 macrophage polarization in patients with HCV infection was mediated by HCVc.…”

Section: Resultsmentioning

confidence: 95%

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HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

Zhang

Wang

Zhai

et al. 2016

Sci Rep

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Hepatitis C virus (HCV) establishes persistent infection in most infected patients, and eventually causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma in some patients. Monocytes and macrophages provide the first line of defense against pathogens, but their roles in HCV infection remains unclear. We have reported that HCV core protein (HCVc) manipulates human blood-derived dendritic cell development. In the present study, we tested whether HCVc affects human blood-derived monocyte differentiating into macrophages. Results showed that HCVc inhibits monocyte differentiation to either M1 or M2 macrophages through TLR2, associated with impaired STATs signaling pathway. Moreover, HCVc inhibits phagocytosis activity of M1 and M2 macrophages, M1 macrophage-induced autologous and allogeneic CD4+ T cell activation, but promotes M2 macrophage-induced autologous and allogeneic CD4+ T cell activation. In conclusion, HCVc inhibits monocyte-derived macrophage polarization via TLR2 signaling, leading to dysfunctions of both M1 and M2 macrophages in chronic HCV infected patients. This may contribute to the mechanism of HCV persistent infection, and suggest that blockade of HCVc might be a novel therapeutic approach to treating HCV infection.

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Section: Resultsmentioning

confidence: 95%

“…Increased level of TLR2 and TLR4 expression were observed in peripheral monocytes of patients with HCV infection, and increased expression of TLR2 is particularly associated with an increase in circulating TNF-α level and hepatic inflammatory activity20. Our previous study showed that HCVc inhibits monocyte differentiation into dendritic cells (DCs)21.…”

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confidence: 99%

HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

Zhang

Wang

Zhai

et al. 2016

Sci Rep

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“…6,7 Briefly, protein-free, phenol-water extracted ultrapure Escherichia coli LPS was used to create a linear standard curve from 1 to 100 pg/ml. HCVc was serially diluted to determine a concentration of agonist within the standard curve of the assay.…”

Section: Limulus Amebocyte Lysate Assay For Detection Of Lps Contaminmentioning

confidence: 99%

“…6,7 T lymphocyte subsets proliferation assays CD8 1 , CD4 1 , CD4 1 CD25 1 Treg and CD4 1 CD25 2 T-cell subsets were stained with 5 mM CFSE (Molecular Probes, Grand Island, NY. USA) according to the manufacturer's recommended protocol.…”

Section: Enzyme-linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

“…6 The HCVc protein also engages TLR2 on human dendritic cells, skewing their differentiation with increased expression of both macrophage markers, and PD-L1. 7 Tregs isolated from HCV-infected patients are immunosuppressive and can inactivate both HCV-specific and bystander CD4 1 and CD8 1 T cells. 8,9 Here, we show that the concentration 1 of HCVc in the blood of HCV-infected patients directly correlates with the frequency of Tregs.…”

Section: Introductionmentioning

confidence: 99%

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Hepatitis C virus core protein triggers expansion and activation of CD4+CD25+ regulatory T cells in chronic hepatitis C patients

Zhai

Chi

et al. 2014

Cell Mol Immunol

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CD4 1 CD25 1 FoxP3 1 regulatory T cells (Tregs) are increased in patients with chronic hepatitis C, which may contribute to the sustained suppression of hepatitis C virus (HCV)-specific T-cell responses and viral persistence in HCV-infected individuals. We postulated that HCV core protein (HCVc) directly contributes to the expansion of Tregs in HCV-infected patients, and we provide evidence to support this hypothesis in the report. Peripheral blood mononuclear cells (PBMCs) and sera were collected from 87 treatment-naïve chronic HCV-infected patients, CD4 1 CD25 1 Tregs were measured by flow cytometry, and HCV RNA and HCVc levels were detected using qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. CD4 1 , CD8 1 , CD4 1 CD25 1 and CD4 1 CD25 2 T cells were purified from healthy donors and cultured with recombinant HCVc and Toll-like receptor (TLR) ligands. Flow cytometry was used to analyze cell proliferation, and ELISA was performed to measure cytokine production. In the 87 chronic HCV-infected patients, HCVc showed a significant correlation with HCV RNA and CD4 1 CD25 1 Tregs. Mechanistic studies showed that HCVc, together with anti-CD3 antibody, augmented CD4 1 CD25 1 Treg proliferation, but inhibited CD4 1 CD25 2 T-cell proliferation and IFN-c production, in a dose-dependent and Treg-dependent manner. Moreover, unlike the TLR3 ligand (poly I:C) and the TLR4 ligand (lipopolysaccharide, LPS), the TLR2 ligand (lipoteichoic acid, LTA) and HCVc both inhibited TCR-induced CD4 1 T-cell proliferation and IFN-c secretion in a Treg-dependent manner. These data indicate that HCVc, like other TLR2 ligands, triggers CD4 1 CD25 1 Treg activation and expansion to inhibit host immune responses, which may play a critical role in viral persistence in HCV-infected patients.

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Coronavirus infections and immune responses

Fan

Lai

et al. 2020

Journal of Medical Virology

1,687

1,776

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Coronaviruses (CoVs) are by far the largest group of known positive-sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV-induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.

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HCV core and NS3 proteins manipulate human blood-derived dendritic cell development and promote Th 17 differentiation

Cited by 28 publications

References 33 publications

HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

Hepatitis C virus core protein triggers expansion and activation of CD4+CD25+ regulatory T cells in chronic hepatitis C patients

Coronavirus infections and immune responses

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