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

Microbes Infect. 2013 Sep-Oct;15(10-11):749-54. doi: 10.1016/j.micinf.2013.05.004. Epub 2013 Jun 20.

Abstract

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.

Keywords: Interferon-gamma (IFNγ); Neutrophil; Peritonitis; Polymorphonuclear leukocyte; Staphylococcus aureus; saeR/S.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Load
  • Bacterial Proteins / immunology*
  • Disease Models, Animal
  • Interferon-gamma / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neutrophils / immunology*
  • Neutrophils / microbiology*
  • Peritonitis / immunology*
  • Peritonitis / microbiology
  • Peritonitis / pathology
  • Protein Kinases / immunology*
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Transcription Factors

Substances

  • Bacterial Proteins
  • SaeR protein, Staphylococcus aureus
  • Transcription Factors
  • Interferon-gamma
  • Protein Kinases
  • SaeS protein, Staphylococcus aureus