Coordinate expression of cytokines and chemokines by NK cells during murine cytomegalovirus infection

被引:99
作者
Dorner, BG
Smith, HRC
French, AR
Kim, S
Poursine-Laurent, J
Beckman, DL
Pingel, JT
Kroczek, RA
Yokoyama, WM
机构
[1] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA
[3] Barnes Jewish Hosp, St Louis, MO 63110 USA
[4] Robert Koch Inst, D-1000 Berlin, Germany
关键词
D O I
10.4049/jimmunol.172.5.3119
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cytokines and chemokines activate and direct effector cells during infection. We previously identified a functional group of five cytokines and chemokines, namely, IFN-gamma, activation-induced T cell-derived and chemokine-related cytokine/lymphotactin, macrophage-inflammatory protein 1alpha, macrophage-inflammatory protein 1beta, and RANTES, coexpressed in individual activated NK cells, CD8(+) T cells, and CD4(+) Th1 cells in vitro and during in vivo infections. However, the stimuli during infection were not known. In murine CMV (MCMV) infection, the DAP12/KARAP-associated Ly49H NK cell activation receptor is crucial for resistance through recognition of MCMV-encoded m157 but NK cells also undergo in vivo nonspecific responses to uncharacterized stimuli. In this study, we show that Ly49H ligation by m157 resulted in a coordinated release of all five cytokines/ chemokines from Ly49H(+) NK cells. Whereas other cytokines also triggered the release of these cytokines/chemokines, stimulation was not confined to the Ly49H(+) population. At the single-cell level, the production of the five mediators showed strong positive correlation with each other. Interestingly, NK cells were a major source of these five cytokines/chemokines in vitro and in vivo, whereas infected macrophages produced only limited amounts of macrophage-inflammatory protein 1alpha, macrophage-inflammatory protein1beta, and RANTES. These findings suggest that both virus-specific and nonspecific NK cells play crucial roles in activating and directing other inflammatory cells during MCMV infection.
引用
收藏
页码:3119 / 3131
页数:13
相关论文
共 58 条
[1]  
Alcamí A, 1998, J IMMUNOL, V160, P624
[2]   Functional interactions between dendritic cells and NK cells during viral infection [J].
Andrews, DM ;
Scalzo, AA ;
Yokoyama, WM ;
Smyth, MJ ;
Degli-Esposti, MA .
NATURE IMMUNOLOGY, 2003, 4 (02) :175-181
[3]   NK1.1+ cells and murine cytomegalovirus infection:: What happens in situ? [J].
Andrews, DM ;
Farrell, HE ;
Densley, EH ;
Scalzo, AA ;
Shellam, GR ;
Degli-Esposti, MA .
JOURNAL OF IMMUNOLOGY, 2001, 166 (03) :1796-1802
[4]   Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors [J].
Arase, H ;
Mocarski, ES ;
Campbell, AE ;
Hill, AB ;
Lanier, LL .
SCIENCE, 2002, 296 (5571) :1323-1326
[5]  
BAGGIOLINI M, 1994, ADV IMMUNOL, V55, P97
[6]   THE ROLE OF NATURAL-KILLER-CELLS IN INNATE RESISTANCE TO INFECTION [J].
BANCROFT, GJ .
CURRENT OPINION IN IMMUNOLOGY, 1993, 5 (04) :503-510
[7]   SEVERE HERPESVIRUS INFECTIONS IN AN ADOLESCENT WITHOUT NATURAL-KILLER CELLS [J].
BIRON, CA ;
BYRON, KS ;
SULLIVAN, JL .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 320 (26) :1731-1735
[8]   Cellular responses to interferon-gamma [J].
Boehm, U ;
Klamp, T ;
Groot, M ;
Howard, JC .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :749-795
[9]   Vital involvement of a natural killer cell activation receptor in resistance to viral infection [J].
Brown, MG ;
Dokun, AO ;
Heusel, JW ;
Smith, HRC ;
Beckman, DL ;
Blattenberger, EA ;
Dubbelde, CE ;
Stone, LR ;
Scalzo, AA ;
Yokoyama, WM .
SCIENCE, 2001, 292 (5518) :934-937
[10]   PATHOGENESIS OF MURINE CYTOMEGALOVIRUS-INFECTION IN NATURAL-KILLER CELL-DEPLETED MICE [J].
BUKOWSKI, JF ;
WODA, BA ;
WELSH, RM .
JOURNAL OF VIROLOGY, 1984, 52 (01) :119-128