Dendritic Cells in Hepatitis C Virus Infection
Ghada Maged Mohsen Hassan;
Abstract
The global prevalence of chronic hepatitis C is estimated at 2.8%. There is markedly higher prevalence in the Middle East and about 14.7% in Egypt.
Chronic infection is indicated by persistent viremia after 12-24 weeks of infection with increased risk of progression to cirrhosis and HCC.
Dendritic cells are one of the major APCs in the body. They bridge innate and adaptive immunity and impact priming of HCV-specific immune responses. DCs rapidly differentiate into mature DCs in response to various “danger” signals like activation through PAMPs in particular TLR ligands, interaction with innate lymphocytes (NK and NKT cells), cytokines, and inflammatory mediators.
There are two main subsets of DCs, mDCs representing the majority of DCs and mostly associated with antigen processing and presentation and pDCs that can sense viral infections and are the main producers of type I and type III IFNs. PDCs can detect HCV RNA in a TLR-7 specific manner. As such, DCs are considered a main orchestrator of the HCV innate and adaptive immune response.
The bidirectional crosstalk between DCs and NK cells has been an interesting field of study both in normal and pathological settings. DCs and NK cells interact with each other through cell-cell contact and membrane bound ligands or by soluble agents synthesized by immune and non-immune cells.
In the current study, we aimed to investigate the DC activation status, and their role in interaction with NK cells utilizing different setups with healthy NK and HCV+ DC, HCV+ NK and healthy DC, healthy DC and healthy NK and finally HCV+ NK and HCV+ DC in the presence of HCV peptides and a ratio of 5 NK: 1DC.
The status of DCs was assessed through studying the surface markers, HLA-DR, CD11c, CD14, CD83, CD86 and annexin.
Our study was an experimental in-vitro study performed on fresh blood bags classified into 2 groups; blood bags from double positive PCR and ELISA HCV antibody donors and blood bags from double negative PCR and ELISA HCV antibody healthy donors. The results of this experiment may differ from what happens in-vivo but gave us a basic idea about NK cell and DC crosstalk.
Our study showed that DC-NK interaction in chronic HCV infection is mainly affected by the affection of DCs by HCV leading to a maturation defect (decreased expression of HLA-DR, CD86 and CD83). This was mainly due to core peptide, to a lesser extent by NS5 whereas there was no effect by NS3-NS4.
Our study also showed that healthy NK cells were able to stimulate the maturation of DCs particularly with core peptide whereas NS3-NS4 had no effect.
It was also evident that when DCs were healthy, all peptides were able to produce significant maturation of DCs even when co-cultured with HCV+ NK cells.
Whereas when both DCs and NK cells were derived from HCV double positive blood bags, there was no increase in HLA-DR except with NS5.
Our experiment also showed that co-cultured HCV+ NK cells and HCV+ DCs showed significantly higher apoptosis of both cells. This could be attributed to the immature state of moDCs found more with chronic HCV infectiondue to the under expression of HLA-class I molecules that would protect from NK-mediated lysis.
Chronic infection is indicated by persistent viremia after 12-24 weeks of infection with increased risk of progression to cirrhosis and HCC.
Dendritic cells are one of the major APCs in the body. They bridge innate and adaptive immunity and impact priming of HCV-specific immune responses. DCs rapidly differentiate into mature DCs in response to various “danger” signals like activation through PAMPs in particular TLR ligands, interaction with innate lymphocytes (NK and NKT cells), cytokines, and inflammatory mediators.
There are two main subsets of DCs, mDCs representing the majority of DCs and mostly associated with antigen processing and presentation and pDCs that can sense viral infections and are the main producers of type I and type III IFNs. PDCs can detect HCV RNA in a TLR-7 specific manner. As such, DCs are considered a main orchestrator of the HCV innate and adaptive immune response.
The bidirectional crosstalk between DCs and NK cells has been an interesting field of study both in normal and pathological settings. DCs and NK cells interact with each other through cell-cell contact and membrane bound ligands or by soluble agents synthesized by immune and non-immune cells.
In the current study, we aimed to investigate the DC activation status, and their role in interaction with NK cells utilizing different setups with healthy NK and HCV+ DC, HCV+ NK and healthy DC, healthy DC and healthy NK and finally HCV+ NK and HCV+ DC in the presence of HCV peptides and a ratio of 5 NK: 1DC.
The status of DCs was assessed through studying the surface markers, HLA-DR, CD11c, CD14, CD83, CD86 and annexin.
Our study was an experimental in-vitro study performed on fresh blood bags classified into 2 groups; blood bags from double positive PCR and ELISA HCV antibody donors and blood bags from double negative PCR and ELISA HCV antibody healthy donors. The results of this experiment may differ from what happens in-vivo but gave us a basic idea about NK cell and DC crosstalk.
Our study showed that DC-NK interaction in chronic HCV infection is mainly affected by the affection of DCs by HCV leading to a maturation defect (decreased expression of HLA-DR, CD86 and CD83). This was mainly due to core peptide, to a lesser extent by NS5 whereas there was no effect by NS3-NS4.
Our study also showed that healthy NK cells were able to stimulate the maturation of DCs particularly with core peptide whereas NS3-NS4 had no effect.
It was also evident that when DCs were healthy, all peptides were able to produce significant maturation of DCs even when co-cultured with HCV+ NK cells.
Whereas when both DCs and NK cells were derived from HCV double positive blood bags, there was no increase in HLA-DR except with NS5.
Our experiment also showed that co-cultured HCV+ NK cells and HCV+ DCs showed significantly higher apoptosis of both cells. This could be attributed to the immature state of moDCs found more with chronic HCV infectiondue to the under expression of HLA-class I molecules that would protect from NK-mediated lysis.
Other data
| Title | Dendritic Cells in Hepatitis C Virus Infection | Other Titles | الخلاياالمتغصنة في عدوى الالتهاب الكبدي الوبائي الفيروسي سي | Authors | Ghada Maged Mohsen Hassan | Issue Date | 2017 |
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