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

Losikoff, Phyllis; Self, Alyssa A.; Gregory, Stephen H.

doi:10.4161/viru.21823

Cited by 43 publications

(37 citation statements)

References 137 publications

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“…Lee et al (2001) demonstrated that HCV core protein, which is either expressed within macrophage cells or exogenously added to them, is capable of suppressing IL-12 production by activated APCs. In addition, HCV core protein was shown to exert an inhibitory effect on the stimulatory capacity of macrophages in mixed lymphocyte reaction (Losikoff et al, 2012). Taken together, these results suggested that HCV core protein could play significant roles in suppressing the effective HCV-specific Th1 immunity through inhibition of IL-12 secretion and inhibition of macrophage functions, which may contribute to persistent HCV infection.…”

Section: Discussionmentioning

confidence: 84%

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis

Hetta

Mekky

Khalil

et al. 2016

Journal of Medical Microbiology

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Extra-hepatic compartments might contribute to hepatitis C virus (HCV) persistence and extrahepatic manifestations. Therefore, we investigated HCV infection in colonic tissue in patients with chronic hepatitis C (CHC) and its relationship with HCV pathogenesis. Colonic biopsies were collected from three groups with CHC infection: treatment naïve (TN; n=12), non-responders (NR; n=10) to anti-HCV therapy (pegylated interferon-a and ribavirin) and sustained virologic response (SVR; n=10) and from a fourth healthy control group (n=10). Liver biopsies were examined to assess inflammation and fibrosis. HCV infection and colonic T regulatory (T reg ) frequency were detected by immunohistochemistry. HCV core and NS3 proteins were detected in B cells and macrophage/monocytes of 42 % and 25 % of TN and 50 % and 30 % of NR, respectively, but not in SVR or control group. The numbers of cells expressing HCV proteins were positively correlated with both HCV viral load and colonic T reg frequency. A significant negative correlation between HCV-expressing cells with both liver inflammation and fibrosis was identified. Our study provides evidence that HCV can infect B cells and macrophages of the colon. The correlations between HCV infection in colonic tissue and HCV viral load and liver pathology underline the significance of this extra-hepatic infection in HCV pathogenesis and response to therapy.

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Section: Discussionmentioning

confidence: 84%

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis

Hetta

Mekky

Khalil

et al. 2016

Journal of Medical Microbiology

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“…Accumulating evidence indicates that patients with chronic viral hepatitis display an increased number of Treg cells in peripheral blood or liver; however, the increment of Treg cells in CHC and their role in liver damage development is still a matter of debate [21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

Valva

Gismondi

Casciato

et al. 2014

Clinical Microbiology and Infection

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Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3(+) and TUNEL(+) hepatocytes, as well as total, CD4(+), CD8(+), Foxp3(+) and CD20(+) lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p 0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3(+) r = 0.74, p < 0.0001; TUNEL(+) r = 0.606, p 0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were associated with the severity of fibrosis. In adults, activated caspase-3(+) cell count was increased in severe hepatitis (p = 0.009). Total, CD4(+), CD8(+) and Foxp3(+) lymphocyte count was higher in adult samples (p < 0.05). Paediatric CD8(+) cells correlated with infected (r = 0.495, p 0.04) and TUNEL(+) hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated caspase-3(+) hepatocytes (r = 0.387, p 0.04). In adults, CD8(+) was associated with hepatitis severity (p < 0.0001) and correlated with inflammatory activity (CD8(+) r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.

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“…Tregs expand during HCV infection in humans and this has been suggested to be involved in the establishment of a persistent infection [7, 62, 63]. CD4 + CD25 + Tregs isolated from HCV-infected patients inhibit antiviral CD8 + T cell responses while depletion of CD4 + Tregs enhances proliferation of remaining T cells [64, 65].…”

Section: Introductionmentioning

confidence: 99%

Regulatory T Cells in Autoimmune and Viral Chronic Hepatitis

Lapierre

Lamarre

2015

Journal of Immunology Research

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In both autoimmune liver disease and chronic viral hepatitis, the injury results from an immune-mediated cytotoxic T cell response to liver cells. As such, it is not surprising that CD4+ regulatory T cells, a key regulatory population of T cells able to curb immune responses, could be involved in both autoimmune hepatitis and chronic viral hepatitis. The liver can induce the conversion of naïve CD4+ T cells to CD4+ regulatory T cells and induce tolerance to locally expressed antigens. This tolerance mechanism is carefully regulated in physiological conditions but any imbalance could be pathological. An overly tolerant immune response can lead to chronic infections while an overreactive and unbridled immune response can lead to autoimmune hepatitis. With the recent advent of monoclonal antibodies able to target regulatory T cells (daclizumab) and improve immune responses and several ongoing clinical trials analysing the impact of regulatory T cell infusion on autoimmune liver disease or liver transplant tolerance, modulation of immunological tolerance through CD4+ regulatory T cells could be a key element of future immunotherapies for several liver diseases allowing restoring the balance between proper immune responses and tolerance.

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

Cited by 43 publications

References 137 publications

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

Regulatory T Cells in Autoimmune and Viral Chronic Hepatitis

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