Early viraemia clearance during antiviral therapy of chronic hepatitis C improves dendritic cell functions

Pachiadakis, Ioannis; Chokshi, Shilpa; Cooksley, Helen; Farmakiotis, Dimitrios; Sarrazin, Christoph; Zeuzem, Stefan; Michalak, Tomasz I.; Naoumov, Nikolai V.

doi:10.1016/j.clim.2009.02.001

Cited by 13 publications

(16 citation statements)

References 45 publications

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“…Circulating pDCs in chronic HCV-infected patients exhibit: diminished HLA-DR expression, a markedly reduced capacity to secrete IFN-α and, consequently, decreased anti-viral potency 36 , 39 , 44 , 67 , 68 , 80 . mDCs in chronic HCV infections secrete significantly lower levels of IL-12 and increased concentrations of IL-10, which tends to skew the immune response toward tolerance and a reduced ability to induce T-cell proliferation and T h1 polarization 36 , 47 , 49 , 67 , 69 , 72 , 75 - 77 , 81 . The stimulatory potential of mDCs and the alloreactive response of CD4 + T cells are also diminished in chronic HCV infections 44 .…”

Section: Contribution Of Dcs To the Pathogenesis Of Hepatitis Cmentioning

confidence: 99%

Dendritic cells, regulatory T cells and the pathogenesis of chronic hepatitis C

2012

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Hepatitis C virus (HCV) is a small, enveloped RNA virus and a major cause of chronic liver disease. Resolution of primary HCV infections depends upon the vigorous responses of CD4+ and CD8+ T cells to multiple viral epitopes. Although such broad-based responses are readily detected early during the course of infection regardless of clinical outcome, they are not maintained in individuals who develop chronic disease. Ostensibly, a variety of factors contribute to the diminished T cell responses observed in chronic, HCV-infected patients including impaired dendritic cell function and the induction of CD4+FoxP3+ regulatory T cells. Overwhelming evidence suggests that the complex interaction of dendritic cells and regulatory T cells plays a critical role in the pathogenesis of chronic hepatitis C.

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Section: Contribution Of Dcs To the Pathogenesis Of Hepatitis Cmentioning

confidence: 99%

Dendritic cells, regulatory T cells and the pathogenesis of chronic hepatitis C

2012

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“…Early HCV clearance upon therapy improves MDC functions [48]; this very fact could be exploited if an HCV vaccine is limited to a specific HCV genotype and adjuvant therapy with ex vivo-manipulated self-derived DCs is considered.…”

Section: Myeloid Dendritic Cellsmentioning

confidence: 99%

“…Baseline chemotaxis of PDCs to CXCL12 and CXCL10 is low and is predictive of failed antiviral response, while correlating with the histological activity index inflammation score [39]. All these defects can be attributed to the presence of HCV RNA in PDCs [55,64], and by the normalization of PDC functions in patients who have cleared the virus upon treatment with antiviral therapy [48,61,62]. Surprisingly PDCs exhibit little susceptibility to viral entry when delivered forcefully or by simple incubation and they are not susceptible to pseudotype VSV-E1E2 entry [65].…”

Section: Plasmacytoid Dendritic Cellsmentioning

confidence: 99%

Dendritic cells in hepatitis C infection: can they (help) win the battle?

Dolganiuc

Szabó

2011

J Gastroenterol

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Infection with hepatitis C virus (HCV) is a public health problem; it establishes a chronic course in ~85% of infected patients and increases their risk for developing liver cirrhosis, hepatocellular carcinoma, and significant extrahepatic manifestations. The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system. Dendritic cells (DCs) are the most efficient inducers of immune responses; they are capable of triggering productive immunity and maintaining the state of tolerance to self- and non-self antigens. During the past decade, multiple research groups have focused on DCs, in hopes of unraveling an HCV-specific DC signature or DC-dependent mechanisms of antiviral immunity which would lead to a successful HCV elimination strategy. This review incorporates the latest update in the current status of knowledge on the role of DCs in anti-HCV immunity as it relates to several challenging questions: (a) the phenotype and function of diverse DC subsets in HCV-infected patients; (b) the characteristics of non-human HCV infection models from the DCs' point of view; (c) how can in vitro systems, ranging from HCV protein- or peptide-exposed DC to HCV protein-expressing DCs, and in vivo systems, ranging from HCV protein-expressing transgenic mice to HCV-infected non-human primates, be employed to dissect the role of DCs in triggering/maintaining a robust antiviral response; and (d) the prospect of DC-based strategy for managing and finding a cure for HCV infection.

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“…Indeed, mDCs isolated from chronically HCV‐infected patients show a reduced capacity to induce a mixed lymphocyte response, impaired maturation and decreased interleukin‐12 (IL‐12) production . Intriguingly, recent studies indicate that treatment with interferon‐ α (IFN‐ α )/ribavirin (RBV) restores the function of mDCs in HCV patients, a finding that correlates with higher antiviral T‐cell responses . However, the mechanisms underlying mDC dysfunction in chronic HCV infection and functional restoration by IFN‐ α ‐based therapy remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Role of A20 in interferon‐α‐mediated functional restoration of myeloid dendritic cells in patients with chronic hepatitis C

Zhou

Zhang

et al. 2014

Immunology

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SummaryHepatitis C virus (HCV) infection is a global health problem characterized by a high rate of chronic infection, which may in part be due to a defect in myeloid dendritic cells (mDCs). This defect appears to be remedied by treatment with interferon-a (IFN-a) -based antiviral therapies; however, the molecular mechanisms underlying mDC dysfunction in HCV infection and restoration by IFN-a treatment are unclear. The ubiquitin-editing protein A20 plays a crucial role in controlling the maturation, cytokine production and immunostimulatory function of mDCs. We propose that the expression of A20 correlates with the function of mDCs during HCV infection and IFN-a therapy. In this study, we observed that A20 expression in mDCs isolated from chronically HCV-infected subjects was significantly higher than healthy subjects or subjects achieving sustained virological responses (SVR) following antiviral treatment. Notably, A20 expression in mDCs from HCV patients during IFN-a treatment was significantly lower than for untreated patients, SVR patients, or healthy subjects. Besides, A20 expression in mDCs stimulated by polyI:C differed between HCV patients and healthy subjects, and this difference could be abrogated by the treatment with IFN-a in vitro. Additionally, A20 expression by polyI:C-activated mDCs, with or without IFN-a treatment, negatively correlated with the expression of HLA-DR, CD86 and CCR7, and the secretion of interleukin-12 (IL-12), but positively associated with the production of IL-10. Importantly, silencing A20 expression using small interfering RNAs increased the production of IL-12 in mDCs of chronically HCV-infected individuals. These findings suggest that A20 plays a crucial role in negative regulation of innate immune responses during chronic viral infection.

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Early viraemia clearance during antiviral therapy of chronic hepatitis C improves dendritic cell functions

Cited by 13 publications

References 45 publications

Dendritic cells, regulatory T cells and the pathogenesis of chronic hepatitis C

Dendritic cells, regulatory T cells and the pathogenesis of chronic hepatitis C

Dendritic cells in hepatitis C infection: can they (help) win the battle?

Role of A20 in interferon‐α‐mediated functional restoration of myeloid dendritic cells in patients with chronic hepatitis C

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