title: The SaeR/S two-component system induces interferon-gamma production in neutrophils during invasive Staphylococcus aureus infection.
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.
authors.affiliation: Montana State University, Department of Immunology and Infectious Diseases, 109 Lewis Hall, Cooley Laboratory, Bozeman, MT 59718, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Watkins
authors.forename: Oliwia W
authors.initials: OW
authors.lastname: Zurek
authors.forename: Kyler B
authors.initials: KB
authors.lastname: Pallister
authors.forename: Jovanka M
authors.initials: JM
authors.lastname: Voyich
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D010538:Peritonitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011494:Protein Kinases / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014157:Transcription Factors
chemical_list: D001426:Bacterial Proteins; C433805:SaeR protein, Staphylococcus aureus; D014157:Transcription Factors; D007371:Interferon-gamma; D011494:Protein Kinases; C527351:SaeS protein, Staphylococcus aureus
keywords: Interferon-gamma (IFNγ); Neutrophil; Peritonitis; Polymorphonuclear leukocyte; Staphylococcus aureus; saeR/S