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Success of antiviral therapy in chronic hepatitis C infection relates to functional status of myeloid dendritic cells.

Rana D, Chawla Y, Arora SK - Indian J. Med. Res. (2013)

Bottom Line: Various immunological factors, both innate and adaptive, play role in the pathogenesis of the disease and become dysfunctional in active disease.Recent reports suggest the major impact of functional and numerical status of dendritic cells in deciding the fate of antiviral therapy.In this review we take a look at the involvement of dendritic cells in playing an important role in the response to therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

ABSTRACT
Chronic hepatitis C infection poses a major global health predicament and appears to be potent threat to mankind. The treatment in wide use is interferon/ribavirin combination therapy which is generally effective in about 60-70 per cent of patients carrying genotype 3 and causes significant morbidity. The response to therapy is largely guided by limited number of factors such as genotype of virus, rapid virological response, ethnicity, pre-therapy viral load, etc. While involvement of host genetic factors has been a major focus of research in playing an important role in the outcome of disease, the role of immune system cannot be marginalized. Poor cellular trafficking and suboptimal T cell responses in liver, the hall marks of chronic hepatitis C virus infection, might be attributed to defective antigen presentation. Various immunological factors, both innate and adaptive, play role in the pathogenesis of the disease and become dysfunctional in active disease. Recent reports suggest the major impact of functional and numerical status of dendritic cells in deciding the fate of antiviral therapy. In this review we take a look at the involvement of dendritic cells in playing an important role in the response to therapy.

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The immune response in viral hepatitis C involves both the innate and adaptive immune system. Innate immunity involves activation of resident liver macrophages (MØ), dendritic cells (DCs), natural killer (NK) cells, and NKT cells, whereas CD4+ T cells, CD8+ T cells, and B lymphocytes are effectors of adaptive immunity. CTL, cytotoxic T lymphocyte; HCV, hepatitis C virus; IFN, interferon; IL, interleukin; MHC, major histocompatibility complex; TNF, tumour necrosis factor.(Reproduced with permission from John Wiley and Sons Ltd., New Jersey, USA [Clin Liver Dis 2006; 10 : 753-71]17.
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Figure 1: The immune response in viral hepatitis C involves both the innate and adaptive immune system. Innate immunity involves activation of resident liver macrophages (MØ), dendritic cells (DCs), natural killer (NK) cells, and NKT cells, whereas CD4+ T cells, CD8+ T cells, and B lymphocytes are effectors of adaptive immunity. CTL, cytotoxic T lymphocyte; HCV, hepatitis C virus; IFN, interferon; IL, interleukin; MHC, major histocompatibility complex; TNF, tumour necrosis factor.(Reproduced with permission from John Wiley and Sons Ltd., New Jersey, USA [Clin Liver Dis 2006; 10 : 753-71]17.

Mentions: While most studies on the human adaptive immune responses against HCV are concentrated on the T cell responses, the role of neutralizing antibodies in the protective immunity against HCV has only recently gained attention3940. Even though there are less number of cases with self-limited HCV infection that have been studied so far, a pattern of vigorous and strong HCV specific T cell response has been observed404142. Such responses were observed only during the early phase of acute disease4143 and sustained for long after the clearance of HCV40. These responses were generally targeted at multiple major histocompatibility complex (MHC) restricted epitopes rather than a dominant epitope42. In contrast, patients with chronic HCV infection usually have weak or defective T cell responses against HCV, as indicated by low frequencies of the specific T cells44 , short-lived responses4445 , narrowly targeted epitopes44 , as well as defects in the effector functions of the specific T cells45. HCV specific CD8+ T cells in chronic hepatitis C patients possess lesser capacity to proliferate and produce lesser amounts of IFNγ in response to HCV antigens46 (Fig. 1).


Success of antiviral therapy in chronic hepatitis C infection relates to functional status of myeloid dendritic cells.

Rana D, Chawla Y, Arora SK - Indian J. Med. Res. (2013)

The immune response in viral hepatitis C involves both the innate and adaptive immune system. Innate immunity involves activation of resident liver macrophages (MØ), dendritic cells (DCs), natural killer (NK) cells, and NKT cells, whereas CD4+ T cells, CD8+ T cells, and B lymphocytes are effectors of adaptive immunity. CTL, cytotoxic T lymphocyte; HCV, hepatitis C virus; IFN, interferon; IL, interleukin; MHC, major histocompatibility complex; TNF, tumour necrosis factor.(Reproduced with permission from John Wiley and Sons Ltd., New Jersey, USA [Clin Liver Dis 2006; 10 : 753-71]17.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928708&req=5

Figure 1: The immune response in viral hepatitis C involves both the innate and adaptive immune system. Innate immunity involves activation of resident liver macrophages (MØ), dendritic cells (DCs), natural killer (NK) cells, and NKT cells, whereas CD4+ T cells, CD8+ T cells, and B lymphocytes are effectors of adaptive immunity. CTL, cytotoxic T lymphocyte; HCV, hepatitis C virus; IFN, interferon; IL, interleukin; MHC, major histocompatibility complex; TNF, tumour necrosis factor.(Reproduced with permission from John Wiley and Sons Ltd., New Jersey, USA [Clin Liver Dis 2006; 10 : 753-71]17.
Mentions: While most studies on the human adaptive immune responses against HCV are concentrated on the T cell responses, the role of neutralizing antibodies in the protective immunity against HCV has only recently gained attention3940. Even though there are less number of cases with self-limited HCV infection that have been studied so far, a pattern of vigorous and strong HCV specific T cell response has been observed404142. Such responses were observed only during the early phase of acute disease4143 and sustained for long after the clearance of HCV40. These responses were generally targeted at multiple major histocompatibility complex (MHC) restricted epitopes rather than a dominant epitope42. In contrast, patients with chronic HCV infection usually have weak or defective T cell responses against HCV, as indicated by low frequencies of the specific T cells44 , short-lived responses4445 , narrowly targeted epitopes44 , as well as defects in the effector functions of the specific T cells45. HCV specific CD8+ T cells in chronic hepatitis C patients possess lesser capacity to proliferate and produce lesser amounts of IFNγ in response to HCV antigens46 (Fig. 1).

Bottom Line: Various immunological factors, both innate and adaptive, play role in the pathogenesis of the disease and become dysfunctional in active disease.Recent reports suggest the major impact of functional and numerical status of dendritic cells in deciding the fate of antiviral therapy.In this review we take a look at the involvement of dendritic cells in playing an important role in the response to therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

ABSTRACT
Chronic hepatitis C infection poses a major global health predicament and appears to be potent threat to mankind. The treatment in wide use is interferon/ribavirin combination therapy which is generally effective in about 60-70 per cent of patients carrying genotype 3 and causes significant morbidity. The response to therapy is largely guided by limited number of factors such as genotype of virus, rapid virological response, ethnicity, pre-therapy viral load, etc. While involvement of host genetic factors has been a major focus of research in playing an important role in the outcome of disease, the role of immune system cannot be marginalized. Poor cellular trafficking and suboptimal T cell responses in liver, the hall marks of chronic hepatitis C virus infection, might be attributed to defective antigen presentation. Various immunological factors, both innate and adaptive, play role in the pathogenesis of the disease and become dysfunctional in active disease. Recent reports suggest the major impact of functional and numerical status of dendritic cells in deciding the fate of antiviral therapy. In this review we take a look at the involvement of dendritic cells in playing an important role in the response to therapy.

Show MeSH
Related in: MedlinePlus