Reduction in the Circulating pDC1/pDC2 Ratio and Impaired Function of Ex Vivo-Generated DC1 In Chronic Hepatitis B Infection

Beckebaum, Susanne; Cicinnati, Vito R.; Dworacki, Grzegorz; Müller-Berghaus, Jan; Stolz, Donna B.; Harnaha, Jo; Whiteside, Theresa L.; Thomson, Angus W.; Lü, Lina; Fung, John J.; Bonham, Clark A.

doi:10.1006/clim.2002.5245

Cited by 103 publications

(112 citation statements)

References 62 publications

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“…In previous studies, possible HBV infection of DC was mostly studied by PCR methods detecting HBV rcDNA genomes 9,10,12 or by PCR in situ hybridization. 31 These methods, however, hardly distinguish input viruses from newly synthesized particles.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8] The role of DC during HBV infection was intensively studied during the last years, but whether total numbers of DC are reduced during chronic infection is discussed controversary. [9][10][11] In some studies, functional deficits of these cells were reported on contact of moDC with HBV, 14 whereas they remained minor in others. 12 Whether the weak or absent T-cell response described in chronic hepatitis B patients results from a defect in the DC compartment, which is caused by the virus itself, is unclear.…”

Section: H Epatitis B Virus (Hbv) Infection Represents Amentioning

confidence: 99%

“…15 Detection of HBV-DNA in DC lysates by polymerase chain reaction (PCR) has been proposed to indicate HBV infection of DC. 9,10,12,13 However, this conclusion can be questioned, because the detection of HBV-DNA and even HBV-RNA in peripheral blood mononuclear cells (PBMC) can be explained by adsorbed virus and does not necessarily correlate with detection of cccDNA and thus with infection. 16 Therefore, whether HBV can infect DC, induce expression of viral antigens, and initiate replication of the viral genome remains unknown.…”

Section: H Epatitis B Virus (Hbv) Infection Represents Amentioning

confidence: 99%

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Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection

et al. 2006

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Dendritic cells (DC) of hepatitis B virus (HBV) carriers have been reported to exhibit functional impairment. Possible explanations for this phenomenon are infection of HBV by DC or alteration of DC function by HBV. We therefore analyzed whether DC support the different steps of HBV infection and replication: uptake, deposition of the HBV genome in the nucleus, antigen expression, and progeny virus release. When HBV genomes were artificially introduced into monocyte-derived DC by adenoviral vectors, low-level expression of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) but no HBV replication was detected. When monocyte-derived DC were subjected to wild-type HBV or a recombinant HBV expressing Renilla luciferase under a non-liver-specific promoter, intracellular HBV DNA was detected in a low percentage of cells. However, neither nuclear cccDNA was formed nor luciferase activity was detected, indicating that either uncoating or nucleocytoplasmic transport were blocked. To verify our observation in the in vivo situation, myeloid and plasmacytoid DC were isolated from blood of high viremic HBV carriers, and analyzed by quantitative polymerase chain reaction (PCR) and electron microscopy. Although circulating DC had in vivo been exposed to more than 10 4 HBV virions per cell, HBV genomic DNA was hardly detected, and no nuclear cccDNA was detected at all. By using electron microscopy, subviral particles were found in endocytic vesicles, but virions were undetectable as were viral capsids in the cytoplasm. H epatitis B virus (HBV) infection represents a major health problem worldwide. Over 350 million individuals are chronically infected with HBV and are at high risk to develop liver cirrhosis or hepatocellular carcinoma. To eliminate the virus after infection, a strong humoral and cellular immune response is required. 1 Thus, control of HBV infection is associated with a multispecific and polyclonal cytotoxic T-cell response and a strong type 1 T helper cell response. 2,3 In contrast, chronically infected patients display oligoclonal T helper cell responses with weak or undetectable cytotoxic T-cell activity. 4 Dendritic cells (DC) are the most important professional antigen-presenting cells. They act as key players in initiating virus-specific T-cell responses. 5 This is reflected by the fact that viruses can evade immune responses by impairing DC function. [6][7][8] The role of DC during HBV infection was intensively studied during the last years, but whether total numbers of DC are reduced during chronic infection is discussed controversary. [9][10][11] In some studies, functional deficits of these cells were reported on contact of moDC with HBV, 14 whereas they remained minor in others. 12 Whether the weak or absent T-cell response described in chronic hepatitis B patients results from a defect in the DC compartment, which is caused by the virus itself, is unclear. Theoretically, numbers or functionality of DC subsets could be affected by interaction of surface receptors on DC with either vi...

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Section: Discussionmentioning

confidence: 99%

Section: H Epatitis B Virus (Hbv) Infection Represents Amentioning

confidence: 99%

Section: H Epatitis B Virus (Hbv) Infection Represents Amentioning

confidence: 99%

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Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection

et al. 2006

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“…However, several reports are available on functional alterations of DC subsets in HBV infection [39], including a report of reduced pDC frequency and reduced expression of TLR9 by pDCs [40]. Liver-infiltrating pDCs are more vulnerable to HBV than their peripheral counterparts; liver pDCs have been reported to be significantly reduced and disabled in non-survivors of acute-on-chronic hepatitis B compared to those in survivors [14].…”

Section: Nk Cells and Dcs In Chronic Hbv 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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“…The purity of DC subsets determined in relation to isotype control was above 95% at 50,000 events acquired. In general, flow cytometry was performed as previously described by one of us (G.D.) [9].…”

Section: Methodsmentioning

confidence: 99%

Significance of Alterations in PBMC Immunophenotype of Children with Chronic Viral Hepatitis C – the Role of Dendritic Cells

et al. 2006

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There are differences in the clinical course of chronic viral hepatitis C between adults and children, but it is generally accepted that the disease has cell-mediated immune background. The aim of this study was to evaluate PBMC subsets in children with chronic hepatitis C before treatment in order to find some predictive factors, useful for patients management. Several PBMC subsets, in particular lymphoid and dendritic cell (DC) ones, were tested by flow cytometry in HCV þ paediatric patients (n ¼ 46) and in control children matched in terms of age and sex (n ¼ 20). Data were subjected to extensive statistics. It was found that cells with cytotoxic potential such as CD8 þ CD28 -T cells, NK and NKT cells as well as lineage -HLA-DR þ DC were increased in per cent values, while CD4 þ T cells and CD4:CD8 ratio were decreased in hepatitis C group. In HCV þ patients, CD4 þ T cells were inversely correlated with alanine aminotransferase (ALT) levels and with viraemia. DC subset of myeloid origin (CD11c þ ) assessed both in per cent values and as mean fluorescence intensity (MFI) of HLA-DR expression was shown to be downregulated in hepatitis patients, in spite of increased numbers. To conclude, PBMC subsets, and in particular DC, are affected by HCV chronic infection in children, reflected by the correlation with clinical parameters, such as ALT and viraemia.

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Reduction in the Circulating pDC1/pDC2 Ratio and Impaired Function of Ex Vivo-Generated DC1 In Chronic Hepatitis B Infection

Cited by 103 publications

References 62 publications

Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection

Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection

Host–virus interactions in hepatitis B and hepatitis C infection

Significance of Alterations in PBMC Immunophenotype of Children with Chronic Viral Hepatitis C – the Role of Dendritic Cells

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