Lipopolysaccharide-mediated mast cell activation induces IFN-gamma secretion by NK cells.
Mast cells (MCs) that are well known for their important effector function in IgE-associated immune responses play a key role in innate immune defenses. In this study, we investigate the interaction between MCs and NK cells in vitro and in vivo. We show that mouse bone marrow-derived cultured MCs activated with LPS, polyinosinic-polycytidylic acid, or CpG can stimulate NK cells to secrete increasing concentrations of IFN-gamma. MCs induce a 20-fold increase in IFN-gamma release from NK cells after LPS stimulation. This enhancement of IFN-gamma secretion is cell contact dependent and TNF-alpha independent. Furthermore, we show that this interaction is in part mediated by OX40 ligand on MCs. NK cell-mediated cytotoxicity was not affected by the presence of MCs. Intracellular IFN-gamma levels in splenic NK cells are significantly decreased after i.p. injection of LPS in mast cell-deficient (C57BL/6 Kit(wsh/wsh)) mice in comparison with wild-type mice. In conclusion, our data show for the first time a direct mast cell-dependent NK cell activation. This interaction might play an important role in innate immune defense, as it is dependent on the presence of stimulators relevant in innate immune responses.
Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
Katja
K
Vosskuhl
Tim F
TF
Greten
Michael P
MP
Manns
Firouzeh
F
Korangy
Jochen
J
Wedemeyer
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000502:physiology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051196:Toll-Like Receptor 3 / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D008070:Lipopolysaccharides; C519703:TLR3 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma