Cutting edge: Overlapping functions of TLR7 and TLR9 for innate defense against a herpesvirus infection

被引:103
作者
Zucchini, Nicolas [1 ,2 ,3 ]
Bessou, Gilles [1 ,2 ,3 ]
Traub, Stephanie [1 ,2 ,3 ]
Robbins, Scott H. [1 ,2 ,3 ]
Uematsu, Satoshi [4 ]
Akira, Shizuo [4 ]
Alexopoulou, Lena [1 ,2 ,3 ]
Dalod, Marc [1 ,2 ,3 ]
机构
[1] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, F-13288 Marseille 09, France
[2] Inst Natl Sante & Rech Med, U 631, Marseille, France
[3] CNRS, UMR 6102, Marseille, France
[4] Osaka Univ, Dept Host Def, Microbial Dis Res Inst, Osaka, Japan
关键词
D O I
10.4049/jimmunol.180.9.5799
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
As initially demonstrated with murine cytomegalovirus (MCMV), plasmacytoid dendritic cells (pDCs) are the major source of IFN-alpha/beta in response to a variety of viruses in vivo. However, contradictory results have been obtained pertaining to the mechanisms promoting IFN-alpha/beta production by pDCs in response to MCMV In this study we show that TLR7 and TLR9 exert redundant functions for IFN-alpha/beta, IL-12p40, and TNF-alpha production by pDCs in vivo during MCMV infection. In contrast, we confirm that systemic production of IL-12p70 strictly depends on TLR9. The combined loss of TLR7 and TLR9 recapitulates critical features of the phenotype of MyD88-deficient mice, including a dramatic decrease in systemic IFN-alpha/beta levels, an increase in viral load, and increased susceptibility to MCMV-induced mortality. This is the first demonstration of the implication of TLR7 in the recognition of a DNA virus.
引用
收藏
页码:5799 / 5803
页数:5
相关论文
共 25 条
[1]   Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].
Adachi, O ;
Kawai, T ;
Takeda, K ;
Matsumoto, M ;
Tsutsui, H ;
Sakagami, M ;
Nakanishi, K ;
Akira, S .
IMMUNITY, 1998, 9 (01) :143-150
[2]   Ikaros is required for plasmacytoid dendritic cell differentiation [J].
Allman, David ;
Dalod, Marc ;
Asselin-Paturel, Carine ;
Delale, Thomas ;
Robbins, Scott H. ;
Trinchieri, Giorgio ;
Biron, Christine A. ;
Kastner, Philippe ;
Chan, Susan .
BLOOD, 2006, 108 (13) :4025-4034
[3]   Interferons α and β as immune regulators -: A new look [J].
Biron, CA .
IMMUNITY, 2001, 14 (06) :661-664
[4]   Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation [J].
Bozza, Silvia ;
Bistoni, Francesco ;
Gaziano, Roberta ;
Pitzurra, Lucia ;
Zelante, Teresa ;
Bonifazi, Pierluigi ;
Perruccio, Katia ;
Bellocchio, Silvia ;
Neri, Mariella ;
Iorio, Anna Maria ;
Salvatori, Giovanni ;
De Santis, Rita ;
Calvitti, Mario ;
Doni, Andrea ;
Garlanda, Cecilia ;
Mantovani, Alberto ;
Romani, Luigina .
BLOOD, 2006, 108 (10) :3387-3396
[5]   Dendritic cell responses to early murine cytomegalovirus infection:: Subset functional specialization and differential regulation by interferon α/β [J].
Dalod, M ;
Hamilton, T ;
Salomon, R ;
Salazar-Mather, TP ;
Henry, SC ;
Hamilton, JD ;
Biron, CA .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (07) :885-898
[6]   MyD88-dependent and -independent murine cytomegalovirus sensing for IFN-α release and initiation of immune responses in vivo [J].
Delale, T ;
Paquin, A ;
Asselin-Paturel, C ;
Dalod, M ;
Brizard, G ;
Bates, EEM ;
Kastner, P ;
Chan, S ;
Akira, S ;
Vicari, A ;
Biron, CA ;
Trinchieri, G ;
Brière, F .
JOURNAL OF IMMUNOLOGY, 2005, 175 (10) :6723-6732
[7]   DAP12 signaling directly augments proproliferative cytokine stimulation of NK cells during viral infections [J].
French, Anthony R. ;
Sjolin, Hanna ;
Kim, Sungjin ;
Koka, Rima ;
Yang, Liping ;
Young, Deborah A. ;
Cerboni, Cristina ;
Tomasello, Elena ;
Ma, Averil ;
Vivier, Eric ;
Karre, Klas ;
Yokoyama, Wayne M. .
JOURNAL OF IMMUNOLOGY, 2006, 177 (08) :4981-4990
[8]   A Toll-like receptor recognizes bacterial DNA [J].
Hemmi, H ;
Takeuchi, O ;
Kawai, T ;
Kaisho, T ;
Sato, S ;
Sanjo, H ;
Matsumoto, M ;
Hoshino, K ;
Wagner, H ;
Takeda, K ;
Akira, S .
NATURE, 2000, 408 (6813) :740-745
[9]   Enhanced green fluorescent protein as a marker for localizing murine cytomegalovirus in acute and latent infection [J].
Henry, SC ;
Schmader, K ;
Brown, TT ;
Miller, SE ;
Howell, DN ;
Daley, GG ;
Hamilton, JD .
JOURNAL OF VIROLOGICAL METHODS, 2000, 89 (1-2) :61-73
[10]   Identification of Lps2 as a key transducer of MyD88-independent TIR signalling [J].
Hoebe, K ;
Du, X ;
Georgel, P ;
Janssen, E ;
Tabeta, K ;
Kim, SO ;
Goode, J ;
Lin, P ;
Mann, N ;
Mudd, S ;
Crozat, K ;
Sovath, S ;
Han, J ;
Beutler, B .
NATURE, 2003, 424 (6950) :743-748