AUTHOR=Guan Zhangchun , Liu Yu , Liu Chenghua , Wang Huiting , Feng Jiannan , Yang Guang 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.658141

DOI=10.3389/fcimb.2021.658141

ISSN=2235-2988

ABSTRACT=<p>IFN-γ is produced upon stimulation with <italic>S. aureus</italic> 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 <italic>S. aureus</italic>, upregulated IFN-γ production by CD56<sup>bright</sup> 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 <italic>S. aureus</italic>.</p>