The SaeR/S two-component system induces interferon-gamma production in neutrophils during invasive Staphylococcus aureus infection

Invasive Staphylococcus aureus (S. aureus) disease is associated with neutrophil activity and pro-inflammatory cytokine expression, including interferon-gamma (IFNγ). Using a mouse model of S. aureus peritonitis, we identify neutrophils as the predominant source of IFNγ and link this induction with the SaeR/S two-component gene regulatory system. Relative to wild-type (BALB/c) mice, IFNγ-deficient mice demonstrated increased bacterial clearance and reduced cellular cytotoxicity following intraperitoneal challenge with S. aureus. Interestingly, bacterial burden and cytotoxicity were similar in BALB/c and IFNγ-deficient mice when infected with an isogenic saeR/S mutant strain. These findings suggest saeR/S-mediated neutrophil-derived IFNγ diminishes innate antibacterial mechanisms against S. aureus.