title: Cross-linking of CD81 by HCV-E2 protein inhibits human intrahepatic plasmacytoid dendritic cells response to CpG-ODN.
abstract: Plasmacytoid dendritic cells (pDCs) are reported to be defective in HCV-infected patients, the mechanisms of which remain poorly understood. We isolated liver derived mononuclear cells (LMNCs) and pDCs from normal liver tissues of benign tumor dissections and liver transplant donors. Isolated pDCs and LMNCs were cultured with precoated HCV envelop protein E2 (HCV-E2) or anti-CD81 mAb in the presence of CpG-ODN. Our results show that cross-linking of CD81 by either HCV-E2 or anti-CD81 mAb inhibits IFN-α secretion in CpG-induced pDCs; down-regulates HLA-DR, CD80 and CD86 expression in pDCs; and suppresses CpG-ODN induced proliferation and survival of pDCs. The blockade of CD81 by soluble anti-CD81 antibody restores pDCs response to CpG-ODN. These results suggest that HCV E2 protein interacts with CD81 to inhibit pDC maturation, activation, and IFN-α production, and may thereby contribute to the impaired innate anti-viral immune response in HCV infection.
authors: Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China. Electronic address: tuzhengkun@hotmail.com.
authors: Zhengkun
authors: Z
authors: Tu
authors: Ping
authors: P
authors: Zhang
authors: Haijun
authors: H
authors: Li
authors: Junqi
authors: J
authors: Niu
authors: Xia
authors: X
authors: Jin
authors: Lishan
authors: L
authors: Su
mesh_terms: D002470:Cell Survival / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D060225:Tetraspanin 28 / Q000037:antagonists & inhibitors / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: C554798:CD81 protein, human; C408982:CPG-oligonucleotide; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins
keywords: CpG oligodeoxynucleotides (CpG-ODN); Cross-linking; Hepatitis C virus envelop protein (HCV-E); Plasmacytoid dendritic cells (pDCs); Toll-like receptor 9 (TLR9)
references: PLoS Biol. 2007 Sep 11;5(10):e248
references: 17850179
references: J Exp Med. 1997 Mar 17;185(6):1101-11
references: 9091583
references: J Immunol. 2004 Apr 15;172(8):4907-16
references: 15067070
references: J Exp Med. 2002 Jan 7;195(1):35-41
references: 11781363
references: PLoS One. 2009;4(2):e4319
references: 19183807
references: J Virol. 2007 Jan;81(1):374-83
references: 17050612
references: Hepatology. 2013 Sep;58(3):940-9
references: 22577054
references: Gut. 2009 Jul;58(7):964-73
references: 19193669
references: Annu Rev Immunol. 2007;25:71-99
references: 17067278
references: Hepatology. 2008 Feb;47(2):385-95
references: 18064579
references: J Exp Med. 2002 Jan 7;195(1):43-9
references: 11781364
references: Science. 1998 Oct 30;282(5390):938-41
references: 9794763
references: Trends Immunol. 2003 Oct;24(10):519-22
references: 14552833
references: Proc Natl Acad Sci U S A. 2004 May 11;101(19):7270-4
references: 15123813
references: Eur J Immunol. 2001 Jan;31(1):166-75
references: 11169450
references: J Immunol. 2010 Apr 15;184(8):4276-83
references: 20304825
references: Blood. 2008 Apr 15;111(8):4245-53
references: 18258799
references: J Infect Dis. 2004 Dec 1;190(11):1919-26
references: 15529255
references: J Clin Invest. 2005 Nov;115(11):3265-75
references: 16224540
references: Cell Immunol. 2011;271(2):286-91
references: 21802664
references: Science. 2004 Mar 5;303(5663):1526-9
references: 14976262
references: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9305-10
references: 10430938
references: Hepatology. 2006 Oct;44(4):945-54
references: 17006905
references: Immunobiology. 2005;210(2-4):237-47
references: 16164031
references: Hepatology. 2004 Aug;40(2):335-45
references: 15368438
references: Eur J Immunol. 2001 Oct;31(10):3026-37
references: 11592079
references: Blood. 2008 Aug 15;112(4):1299-307
references: 18541725
references: Nat Immunol. 2004 Feb;5(2):190-8
references: 14716310
references: J Hepatol. 2007 Sep;47(3):338-47
references: 17467113
references: Annu Rev Immunol. 1998;16:89-109
references: 9597125
references: J Exp Med. 2008 Jan 21;205(1):233-44
references: 18195076
references: Clin Exp Immunol. 2007 Jul;149(1):186-93
references: 17511774
references: Gastroenterology. 2010 Jan;138(1):305-14
references: 19769973