Human mast cell activation with virus-associated stimuli leads to the selective chemotaxis of natural killer cells by a CXCL8-dependent mechanism.
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 (NK) 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 NK cells to sites of early viral infection via CXCL8.
Burke
Sarah M
SM
Dalhousie Inflammation group, Dalhousie University, Halifax, NS.
Issekutz
Thomas B
TB
Mohan
Karkada
K
Lee
Patrick W K
PW
Shmulevitz
Maya
M
Marshall
Jean S
JS
D000998:Antiviral Agents / Q000494:pharmacology; D019002:CD56 Antigen / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D012089:Mammalian orthoreovirus 3; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000821:virology*; D011070:Poly I-C / Q000494:pharmacology; D054367:Receptors, CXCR3 / Q000378:metabolism; D012088:Reoviridae Infections / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000998:Antiviral Agents; D019002:CD56 Antigen; C508606:CXCL8 protein, human; C515187:CXCR3 protein, human; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D054367:Receptors, CXCR3; D011070:Poly I-C