Human mast cell activation with virus-associated stimuli leads to the selective chemotaxis of natural killer cells by a CXCL8-dependent mechanism

被引:92
作者
Burke, Sarah M. [1 ,2 ]
Issekutz, Thomas B. [2 ,4 ]
Mohan, Karkada [2 ,3 ]
Lee, Patrick W. K. [1 ]
Shmulevitz, Maya [1 ]
Marshall, Jean S. [1 ,2 ,4 ]
机构
[1] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS B3H 1X5, Canada
[2] Dalhousie Univ, Dalhousie Inflammat Grp, Halifax, NS B3H 1X5, Canada
[3] Dalhousie Univ, Dept Pediat, Halifax, NS B3H 1X5, Canada
[4] Dalhousie Univ, Dept Pathol, Halifax, NS B3H 1X5, Canada
关键词
D O I
10.1182/blood-2007-10-118547
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Human mast cells are found in skin and mucosal surfaces and next to blood vessels. They play a sentinel cell role in immunity, recognizing invading pathogens and producing proinflammatory mediators. Mast cells can recruit granulocytes, and monocytes in allergic disease and bacterial infection, but their ability to recruit antiviral effector cells such as natural killer (INK) cells and T cells has not been fully elucidated. To investigate the role of human mast cells in response to virus-associated stimuli, human cord blood-derived mast cells (CBMCs) were stimulated with polyinosinic-polycytidylic acid, a double-stranded RNA analog, or infected with the double-stranded RNA virus, reovirus serotype 3 Dearing for 24 hours. CBMCs responded to stimulation with polyinosinic-polycytidylic acid by producing a distinct chemokine profile, including CCL4, CXCL8, and CXCL10. CBMCs produced significant amounts of CXCL8 in response to low levels of reovirus infection, while both skin- and lung-derived fibroblasts were unresponsive unless higher doses of reovirus were used. Supernatants from CBMCs infected with reovirus induced substantial NK cell chemotaxis that was highly dependent on CXCL8 and CXCR1. These results suggest a novel role for mast cells in the recruitment of human INK cells to sites of early viral infection via CXCL8.
引用
收藏
页码:5467 / 5476
页数:10
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