Plasmacytoid dendritic cells in acute and chronic hepatitis C virus infection.
Chronic evolution of acute hepatitis C (aHC) occurs in more than 80% of patients but can frequently be prevented by early treatment with interferon (IFN)-alpha. Plasmacytoid dendritic cells (pDCs) are the major endogenous IFN-alpha producers, but their role in aHC is unknown. In this study, frequency, phenotype, and pDC function were analyzed in 13 patients with aHC and 32 patients with chronic hepatitis C (cHC) compared with 20 healthy controls, 33 sustained responders to antiviral treatment, 14 patients with acute hepatitis B (aHB), and 21 patients with nonviral inflammatory disease. In aHC, pDCs in the peripheral blood were significantly reduced compared with healthy controls (median, 0.1% vs. 0.36%, P < .0005) and were inversely correlated to alanine aminotransferase levels (r = -0.823; P < .005). Circulating pDCs in aHC were immature, as determined via reduced expression of HLA-DR and CCR7, and produced little amounts of IFN-alpha (median, 3.5 pg/50,000 peripheral blood mononuclear cells [PBMCs] vs. 498.4 pg/50,000 PBMCs in healthy controls; P < .0005). Less pronounced changes were present in cHC (median, 0.17%, 28.0 pg/50,000 PBMCs IFN-alpha, respectively). However, a significantly reduced frequency and IFN-alpha production was also found in self-limited aHB (median 0.1%, 8.6 pg/50,000 PBMCs) and in patients with nonviral inflammatory disease (median 0.19%, 7.5 pg/50,000 PBMCs). In conclusion, in aHC frequency and IFN-alpha-producing capacity of peripheral blood pDCs are dramatically reduced and inversely correlated with the degree of liver inflammation. In cHC there is incomplete recovery of pDC function, which, however, could be solely due to the chronic inflammatory state.
Ulsenheimer
Axel
A
Institute for Immunology, Klinikum Grosshadern, University of Munich, Munich, Germany. axel@ulsenheimer.de
Gerlach
J Tilman
JT
Jung
Maria-Christina
MC
Gruener
Norbert
N
Wächtler
Martin
M
Backmund
Markus
M
Santantonio
Teresa
T
Schraut
Winfried
W
Heeg
Malte H J
MH
Schirren
Carl A
CA
Zachoval
Reinhart
R
Pape
Gerd R
GR
Diepolder
Helmut M
HM
D000208:Acute Disease; D000328:Adult; D000368:Aged; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006526:Hepatitis C / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis
C515370:CCR7 protein, human; D006684:HLA-DR Antigens; D016898:Interferon-alpha; D054400:Receptors, CCR7; D019707:Receptors, Chemokine