Hepatitis C is associated with perturbation of intrahepatic myeloid and plasmacytoid dendritic cell function.
OBJECTIVE
In most cases infection with hepatitis C results in chronic infection as a consequence of viral subversion and failed anti-viral immune responses. The suggestion that dendritic cells are defective in chronic HCV infection led us to investigate the phenotype and function of liver-derived myeloid (mDC) and plasmacytoid (pDC) dendritic cells in patients with chronic HCV infection.


METHODS
Liver DCs were isolated without expansion in cytokines from human liver allowing us to study unmanipulated tissue-resident DCs ex vivo.


RESULTS
Compared with mDCs isolated from non-infected inflamed liver mDCs from HCV-infected liver (a) demonstrated higher expression of MHC class II, CD86 and CD123, (b) were more efficient stimulators of allogeneic T-cells and (c) secreted less IL-10. Reduced IL-10 secretion may be a factor in the enhanced functional properties of mDCs from HCV infected liver because antibody depletion of IL-10 enhanced the ability of mDCs from non-infected liver to stimulate T-cells. In contrast, pDCs were present at lower frequencies in HCV-infected liver and expressed higher levels of the regulatory receptor BDCA-2.


CONCLUSIONS
In HCV-infected liver the combination of enhanced mDC function and a reduced number of pDCs may contribute to viral persistence in the face of persistent inflammation.
Lai
Wai Kwan
WK
Liver Research Group, Institute of Biomedical Research, The University of Birmingham Medical School, Wolfson Drive, Edgbaston, Birmingham B15 2TT, UK. w.k.lai@bham.ac.uk
Curbishley
Stuart M
SM
Goddard
Sarah
S
Alabraba
Edward
E
Shaw
Jean
J
Youster
Janine
J
McKeating
Jane
J
Adams
David H
DH
D000906:Antibodies / Q000494:pharmacology; D051940:B7-2 Antigen / Q000032:analysis; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D042381:Granulocyte Precursor Cells / Q000276:immunology / Q000473:pathology; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D053650:Interleukin-3 Receptor alpha Subunit / Q000032:analysis; D037181:Lectins, C-Type / Q000032:analysis; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D011971:Receptors, Immunologic / Q000032:analysis; D013601:T-Lymphocytes / Q000473:pathology
D000906:Antibodies; D051940:B7-2 Antigen; C443299:CLEC4C protein, human; D000949:Histocompatibility Antigens Class II; D053650:Interleukin-3 Receptor alpha Subunit; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D016753:Interleukin-10