Staphylococcus aureus β-Hemolysin Up-Regulates the Expression of IFN-γ by Human CD56bright NK Cells

Abstract

IFN-γ is produced upon stimulation with <i>S. aureus</i> and may play a detrimental role during infection. However, whether hemolysins play a role in the mechanism of IFN-γ production has not been fully characterized. In this study, we demonstrated that Hlb, one of the major hemolysins of <i>S. aureus</i>, upregulated IFN-γ production by CD56^bright NK cells from human peripheral blood mononuclear cells (PBMCs). Further investigation showed that Hlb increased calcium influx and induced phosphorylation of ERK1/2. Either blocking calcium or specifically inhibiting phosphorylation of ERK1/2 decreased the production of IFN-γ induced by Hlb. Moreover, we found that this process was dependent on the sphingomyelinase activity of Hlb. Our findings revealed a novel mechanism of IFN-γ production in NK cells induced by Hlb, which may be involved in the pathogenesis of <i>S. aureus</i>.