Human cytomegalovirus suppresses type I interferon secretion by plasmacytoid dendritic cells through its interleukin 10 homolog

被引:55
作者
Chang, W. L. William [1 ]
Barry, Peter A. [1 ]
Szubin, Richard [1 ,2 ]
Wang, Dai [3 ]
Baumgarth, Nicole [1 ,2 ]
机构
[1] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA
[2] Univ Calif San Francisco, Sch Dent, Dept Cell & Tissue Biol, San Francisco, CA 94154 USA
[3] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
基金
美国国家卫生研究院;
关键词
Human cytomegalovirus; Interleukin; 10; Type I interferons; Plasmacytoid dendritic cells; CD8(+) T-CELLS; REGULATORY FACTOR-3; B-CELLS; DIFFERENTIAL REGULATION; INHIBITS MATURATION; POSITIVE FEEDBACK; CUTTING EDGE; RESPONSES; RECEPTOR; INNATE;
D O I
10.1016/j.virol.2009.05.013
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Type I interferons (IFNs) are innate cytokines with potent antiviral and immunoregulatory activities. It remains unclear how human cytomegalovirus (HCMV) can establish persistence in the face of these strongly antagonistic cytokines. In this study, we confirm that IFN-alpha efficiently suppresses the penetration of HCMV into susceptible cells, including monocytes, the major cell population in peripheral blood that is highly susceptible to HCMV infection. We further demonstrate that the HCMV-derived interleukin 10 (IL-10) homolog functions similar to cellular IL-10 and broadly inhibits TLR-induced transcriptional activation of IFN-alpha/beta genes in plasmacytoid dendritic cells (PDCs), a major type I IFN-producer in vivo that is highly resistant to HCMV infection in vitro. These results suggest that HCMV subverts innate immunity by suppressing type I IFN production of PDCs during primary viral infection via its IL-10 homolog. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:330 / 337
页数:8
相关论文
共 62 条
[1]   Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the interferon response [J].
Abate, DA ;
Watanabe, S ;
Mocarski, ES .
JOURNAL OF VIROLOGY, 2004, 78 (20) :10995-11006
[2]   Cutting edge: CD8 T cells specific for lymphocytic choriomeningitis virus require type IIFN receptor for clonal expansion [J].
Aichele, P ;
Unsoeld, H ;
Koschella, M ;
Schweier, O ;
Kalinke, U ;
Vucikuja, S .
JOURNAL OF IMMUNOLOGY, 2006, 176 (08) :4525-4529
[3]   Human cytomegalovirus impairs dendritic cell function:: a novel mechanism of human cytomegalovirus immune escape [J].
Beck, K ;
Meyer-König, U ;
Weidmann, M ;
Nern, C ;
Hufert, FT .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (06) :1528-1538
[4]   HCMV infection of PDCs deviates the NK cell response into cytokine-producing cells unable to perform cytotoxicity [J].
Cederarv, Madeleine ;
Soderberg-Naucler, Cecilia ;
Odeberg, Jenny .
IMMUNOBIOLOGY, 2009, 214 (05) :331-341
[5]   Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon [J].
Cella, M ;
Jarrossay, D ;
Facchetti, F ;
Alebardi, O ;
Nakajima, H ;
Lanzavecchia, A ;
Colonna, M .
NATURE MEDICINE, 1999, 5 (08) :919-923
[6]   Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon [J].
Cervantes-Barragan, Luisa ;
Zuest, Roland ;
Weber, Friedernann ;
Spiegel, Martin ;
Lang, Karl S. ;
Akira, Shizuo ;
Thiel, Volker ;
Ludewig, Burkhard .
BLOOD, 2007, 109 (03) :1131-1137
[7]   Exposure of myeloid dendritic cells to exogenous or endogenous IL-10 during maturation determines their longevity [J].
Chang, W. L. William ;
Baumgarth, Nicole ;
Eberhardt, Meghan K. ;
Lee, C. Y. Daniel ;
Baron, Colin A. ;
Gregg, Jeff P. ;
Barry, Peter A. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (12) :7794-7804
[8]   Influenza virus infection causes global respiratory tract B cell response modulation via innate immune signals [J].
Chang, W. L. William ;
Coro, Elizabeth S. ;
Rau, Friederike C. ;
Xiao, Yuanyuan ;
Erle, David J. ;
Baumgarth, Nicole .
JOURNAL OF IMMUNOLOGY, 2007, 178 (03) :1457-1467
[9]   A recombinant rhesus cytomegalovirus expressing enhanced green fluorescent protein retains the wild-type phenotype and pathogenicity in fetal macaques [J].
Chang, WLW ;
Tarantal, AF ;
Zhou, SS ;
Borowsky, AD ;
Barry, PA .
JOURNAL OF VIROLOGY, 2002, 76 (18) :9493-9504
[10]   Human cytomegalovirus-encoded interleukin-10 homolog inhibits maturation of dendritic cells and alters their functionality [J].
Chang, WLW ;
Baumgarth, N ;
Yu, D ;
Barry, PA .
JOURNAL OF VIROLOGY, 2004, 78 (16) :8720-8731