PMID- 22093032
OWN - NLM
STAT- MEDLINE
DCOM- 20120307
LR  - 20181201
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Linking)
VI  - 18
IP  - 12
DP  - 2011 Dec
TI  - Chronic hepatitis C infection blocks the ability of dendritic cells to secrete 
      IFN-alpha and stimulate T-cell proliferation.
PG  - 840-51
LID - 10.1111/j.1365-2893.2010.01384.x [doi]
AB  - Dendritic cells (DCs) are likely to play a key role in the compromised T-cell 
      function associated with hepatitis C Virus (HCV) infection. However, studies of 
      DC function in HCV-infected patients to date have yielded conflicting findings 
      possibly because of patient and virus heterogeneity. Here, we report the 
      characterization of monocyte-derived DCs obtained from a homogenous cohort of 
      women who were infected with HCV genotype 1b following exposure to contaminated 
      anti-D immunoglobulin from a single donor source. Patients included in the study 
      had not received anti-viral therapy and all had mild liver disease. We show that 
      phenotypically normal monocyte-derived dendritic cells (MDDCs) (CD11c(+) HLA(-) 
      DR(+) CD1a(+) CD14(lo) ) can be obtained from these patients. These cells respond 
      to both Poly(I:C) and LPS, by up-regulating expression of CD86. They secrete high 
      levels of IL-8 and CCL5 in response to LPS, an indication that the 
      MyD88-dependent and MyD88-independent signalling pathways downstream of TLR4 
      ligation are functioning normally. However, these cells are poor stimulators of 
      T-cell proliferation in allogeneic mixed lymphocyte reactions. Furthermore, 
      patient MDDCs fail to secrete IFN-alpha in response to poly(I:C) or IFN-beta 
      stimulation. Altered DC function may contribute to impaired cellular immune 
      responses and chronicity of disease following HCV infection in this cohort. An 
      effective therapeutic vaccine for chronic HCV infection will most likely need to 
      target DCs to elicit an appropriate cellular response; therefore, it is important 
      to resolve how the DCs of different patient cohorts respond to stimulation via 
      TLRs.
CI  - (c) 2011 Blackwell Publishing Ltd.
FAU - Ryan, E J
AU  - Ryan EJ
AD  - School of Biochemistry and Immunology, Trinity College, Dublin 2 National Liver 
      Transplantation Unit, St. Vincent's Hospital, Dublin 4, Ireland. 
      Elizabeth.Ryan.1@ucdconnect.ie
FAU - Stevenson, N J
AU  - Stevenson NJ
FAU - Hegarty, J E
AU  - Hegarty JE
FAU - O'Farrelly, C
AU  - O'Farrelly C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110314
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (Interferon-alpha)
SB  - IM
MH  - Aged
MH  - *Cell Proliferation
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Hepatitis C, Chronic/*immunology/*pathology
MH  - Humans
MH  - Immune Tolerance
MH  - Interferon-alpha/*metabolism
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes/*immunology
EDAT- 2011/11/19 06:00
MHDA- 2012/03/08 06:00
CRDT- 2011/11/19 06:00
PHST- 2011/11/19 06:00 [entrez]
PHST- 2011/11/19 06:00 [pubmed]
PHST- 2012/03/08 06:00 [medline]
AID - 10.1111/j.1365-2893.2010.01384.x [doi]
PST - ppublish
SO  - J Viral Hepat. 2011 Dec;18(12):840-51. doi: 10.1111/j.1365-2893.2010.01384.x. 
      Epub 2011 Mar 14.