Virus-infected human mast cells enhance Natural Killer cell functions (VIR1P.1160)

Abstract Mast cells are widely distributed throughout vascularised tissues. At mucosal surfaces they play important roles in host defence. Human mast cells produce chemokines, such as CXCL8, that selectively recruit Natural Killer (NK) cells in models of viral infection. However, the ability of mast cells to enhance NK cell effector functions has not been previously examined. Primary human mast cells were infected with reovirus and derived mast cell products were used for stimulation of human NK cells. Mast cell products induced expression of the activation marker CD69 (n=7; p<0.001), the cytotoxicity-related genes PRF1 (n=6; p<0.01) and TIA-1 (n=5; p<0.05), and enhanced NK cell cytotoxic activity against K562 cells (n=6; p<0.01). Interferon-γ was produced by NK cells treated with virus-induced mast cell mediators in the presence of IL-18 (n=7; p<0.001). In vivo, reovirus-infected human mast cells induced a 7-fold increase in recruitment and activated murine NK cells (42.3% CD69+ vs 5.8% CD69+ cells) in comparison to uninfected mast cells in a subcutaneous matrigel model (n=9; p<0.05). Soluble products of reovirus-infected mast cells included IL-10, type I and type III interferons. Blockade of type I interferon receptors revealed that they were important for mast cell-mediated NK cell activation. Our data define a novel mast cell-NK cell immune axis in human host defense against viral infection, which could be rapidly induced prior to the generation of acquired immunity.