title: Superantigens subvert the neutrophil response to promote abscess formation and enhance Staphylococcus aureus survival in vivo.
abstract: Staphylococcus aureus is a versatile bacterial pathogen that produces T cell-activating toxins known as superantigens (SAgs). Although excessive immune activation by SAgs can induce a dysregulated cytokine storm as a component of what is known as toxic shock syndrome (TSS), the contribution of SAgs to the staphylococcal infection process is not well defined. Here, we evaluated the role of the bacterial superantigen staphylococcal enterotoxin A (SEA) in a bacteremia model using humanized transgenic mice expressing SAg-responsive HLA-DR4 molecules. Infection with S. aureus Newman induced SEA-dependent Vβ skewing of T cells and enhanced bacterial survival in the liver compared with infection by sea knockout strain. SEA-induced gamma interferon, interleukin-12, and chemokine responses resulted in increased infiltration of CD11b(+) Ly6G(+) neutrophils into the liver, promoting the formation of abscesses that contained large numbers of viable staphylococci. Hepatic abscesses occurred significantly more frequently in S. aureus Newman-infected livers than in livers infected with the Newman sea knockout strain, promoting the survival of S. aureus in vivo. This represents a novel mechanism during infection whereby S. aureus utilizes SAgs to form a specialized niche and manipulate the immune system.
authors.affiliation: Department of Microbiology and Immunology, Western University, London, Canada.
authors.forename: Stacey X
authors.initials: SX
authors.lastname: Xu
authors.affiliation: Department of Anatomy and Cell Biology, Western University, London, Canada.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Gilmore
authors.affiliation: Department of Microbiology and Immunology, Western University, London, Canada.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Szabo
authors.affiliation: Department of Microbiology and Immunology, Western University, London, Canada.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Zeppa
authors.affiliation: Department of Microbiology and Immunology, Western University, London, Canada Lawson Health Research Institute, London, Canada.
authors.forename: Miren L
authors.initials: ML
authors.lastname: Baroja
authors.affiliation: Department of Microbiology and Immunology, Western University, London, Canada Centre for Human Immunology, Western University, London, Canada Lawson Health Research Institute, London, Canada.
authors.forename: S M Mansour
authors.initials: SM
authors.lastname: Haeryfar
authors.affiliation: Department of Microbiology and Immunology, Western University, London, Canada Centre for Human Immunology, Western University, London, Canada Lawson Health Research Institute, London, Canada john.mccormick@uwo.ca.
authors.forename: John K
authors.initials: JK
authors.lastname: McCormick
mesh_terms: D000038:Abscess / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D004768:Enterotoxins; D015804:HLA-DR4 Antigen; C480309:Ly6G antigen, mouse; D018089:Superantigens; D018664:Interleukin-12; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma