Functional changes, increased apoptosis, and diminished nuclear factor–κB activity of myeloid dendritic cells during chronic hepatitis C infection

Zhao, Li; Shields, Justin; Tyrrell, D. Lorne

doi:10.1016/j.humimm.2010.05.006

Cited by 8 publications

(4 citation statements)

References 43 publications

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“…Since all these cellular receptors are located on the surface of the membrane, possess intracellular signaling domains, and are implicated in cell activation, it is conceivable that, regardless of their capacity to uptake HCV protein, they could lead to DC activation. Indeed, in vitro, individual HCV proteins, core, NS3, NS4, and NS5, as well as fused HCV polyprotein (core-NS3-NS4), were found to impair the functions of both immature and mature DCs by regulating the expression of co-stimulatory and antigen-presentation molecules, inducing the expression of FasL to mediate apoptosis, interfering with allostimulatory capacity, inhibiting TLR signaling, and inhibiting the nuclear translocation of nuclear factor (NF) jB [84,[93][94][95], features which largely reproduce the defects seen in DCs from HCV-infected individuals [42,84,96]. Interestingly, HCV proteins did not directly inhibit T-cell proliferation [94], thus indicating that HCV proteins impair T-cell responses indirectly via inhibiting DCs.…”

Section: Effect Of Hcv Virions On Dcsmentioning

confidence: 98%

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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Section: Effect Of Hcv Virions On Dcsmentioning

confidence: 98%

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

Dolganiuc

Szabó

2011

J Gastroenterol

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“…One of the proposed explanations for these changes effect is enhanced apoptosis in DCs, partly due to diminished NF-jB activity [81]. Dysfunctional DCs are involved in the exhaustion of CD8 ?…”

Section: Dcs In Chronic Hcv Infectionmentioning

confidence: 99%

Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-k3), remains to be elucidated. Human BDCA3 ? DCs have also been shown to be a potent producer of IFN-k3 in HCV infection, suggesting the possibility that BDCA3 ? DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection.

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“…Decreased frequencies of DC during HIV infection can be caused by migration of these cells to the lymphoid tissue or the apoptosis of circulating DC [8][9][10]. In HCV infection, there is evidence for increased homing of DC to the liver [36] or increased apoptosis of DC [37][38][39], which may explain the loss of these cells from the peripheral blood.…”

Section: Discussionmentioning

confidence: 99%

Increased proportions of dendritic cells and recovery of IFNγ responses in HIV/HCV co-infected patients receiving ART

et al. 2016

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Dendritic cell (DC) numbers and functions can be affected by HIV and HCV disease, but the effects of antiretroviral therapy (ART) on DC and the implications of these changes are unclear. We examined circulating DC in samples from Indonesian patients beginning ART with advanced HIV disease and documented mild/moderate HCV hepatitis. Frequencies of myeloid and plasmacytoid DC increased after 6 months on ART, but frequencies of DC producing IL-12 or IFNα following stimulation with TLR agonists (CL075, CpG) did not change. IFNγ responses to CL075, HCV and other antigens rose over this period. Hence increased IFNγ responses during ART may be associated with increased DC frequencies rather than changes in their functional capacity.

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Functional changes, increased apoptosis, and diminished nuclear factor–κB activity of myeloid dendritic cells during chronic hepatitis C infection

Cited by 8 publications

References 43 publications

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

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

Host–virus interactions in hepatitis B and hepatitis C infection

Increased proportions of dendritic cells and recovery of IFNγ responses in HIV/HCV co-infected patients receiving ART

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