PMID- 17881511
OWN - NLM
STAT- MEDLINE
DCOM- 20080123
LR  - 20201212
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 82
IP  - 6
DP  - 2007 Dec
TI  - HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of 
      CD4+ T cells via suppression of dendritic cell IL-12 production.
PG  - 1407-19
AB  - Dendritic cells (DCs) isolated from patients with chronic hepatitis C virus (HCV) 
      infection display an impaired capacity to generate type 1 CD4(+) T cell immunity. 
      Several reports have described an immunomodulatory function for the HCV core 
      protein, and circulating core has been shown to associate with the putative gC1q 
      receptor, gC1qR, expressed on host immune cells. However, the molecular 
      mechanism(s) of HCV core-mediated DC dysfunction has not been defined. Herein, 
      ligation of gC1qR on human monocyte-derived DCs (MDDCs) with HCV core or 
      anti-gC1qR agonist antibody was shown to inhibit TLR-induced IL-12 production but 
      not the production of other TLR-stimulated cytokines. Furthermore, engagement of 
      gC1qR on MDDCs resulted in reduced IFN-gamma secretion by allogeneic CD4(+) T 
      lymphocytes during mixed lymphocyte culture. Differentiation of CD4(+) T cells 
      cocultured with HCV core- or anti-gC1qR antibody-treated MDDCs was also skewed 
      toward production of Th2 cytokines, including IL-4. Importantly, that addition of 
      IL-12 rescued IFN-gamma production and Th1 differentiation by CD4(+) T cells. 
      Therefore, engagement of gC1qR on DCs by HCV core limits the induction of Th1 
      responses and may contribute to viral persistence.
FAU - Waggoner, Stephen N
AU  - Waggoner SN
AD  - Department of Microbiology, Beirne Carter Center for Immunology Research, 
      University of Virginia, Charlottesville, Virginia 22903, USA
FAU - Hall, Caroline H T
AU  - Hall CH
FAU - Hahn, Young S
AU  - Hahn YS
LA  - eng
GR  - T32 AI007046/AI/NIAID NIH HHS/United States
GR  - AI057591/AI/NIAID NIH HHS/United States
GR  - 5T32AI10749608/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070919
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (C1QBP protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Viral Core Proteins)
RN  - 0 (nucleocapsid protein, Hepatitis C virus)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Carrier Proteins/*metabolism
MH  - *Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Dendritic Cells/cytology/drug effects/*immunology
MH  - Humans
MH  - Interleukin-12/*biosynthesis
MH  - Lymphocyte Culture Test, Mixed
MH  - Mitochondrial Proteins/*metabolism
MH  - Monocytes/cytology/drug effects
MH  - Phenotype
MH  - Protein Binding
MH  - Recombinant Proteins/pharmacology
MH  - Th1 Cells/*cytology/drug effects
MH  - Th2 Cells/cytology/drug effects
MH  - Toll-Like Receptors/immunology
MH  - Viral Core Proteins/*metabolism
EDAT- 2007/09/21 09:00
MHDA- 2008/01/24 09:00
CRDT- 2007/09/21 09:00
PHST- 2007/09/21 09:00 [pubmed]
PHST- 2008/01/24 09:00 [medline]
PHST- 2007/09/21 09:00 [entrez]
AID - jlb.0507268 [pii]
AID - 10.1189/jlb.0507268 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2007 Dec;82(6):1407-19. doi: 10.1189/jlb.0507268. Epub 2007 Sep 
      19.