4.7 Article

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

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2021.658141

Keywords

S; aureus; β -hemolysin; IFN-γ CD56(bright) NK cells; ERK; calcium

Funding

  1. National Natural Science Foundation of China [81871618]
  2. Shandong Provincial Major Scientific and Technological Innovation Project (MSTIP) [2019JZZY011012]

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The study demonstrates that the hemolysin Hlb of S. aureus can upregulate IFN-gamma production in target cells by increasing calcium influx and inducing phosphorylation of ERK1/2. This process is dependent on the sphingomyelinase activity of Hlb.
IFN-gamma is produced upon stimulation with S. aureus and may play a detrimental role during infection. However, whether hemolysins play a role in the mechanism of IFN-gamma production has not been fully characterized. In this study, we demonstrated that Hlb, one of the major hemolysins of S. aureus, upregulated IFN-gamma 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-gamma 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-gamma production in NK cells induced by Hlb, which may be involved in the pathogenesis of S. aureus.

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