title: Swift Intrahepatic Accumulation of Granulocytic Myeloid-Derived Suppressor Cells in a Humanized Mouse Model of Toxic Shock Syndrome.
abstract: Toxic shock syndrome (TSS) and other superantigen-mediated illnesses are associated with 'systemic' immunosuppression that jeopardizes the host's ability to fight pathogens. Here, we define a novel mechanism of 'local' immunosuppression that may benefit the host. Systemic exposure to staphylococcal enterotoxin B (SEB) rapidly and selectively recruited CD11b(+)Gr-1(high)Ly-6C(+) granulocytic myeloid-derived suppressor cells (MDSCs) to the liver of HLA-DR4 transgenic mice. Hepatic MDSCs inhibited SEB-triggered T cell proliferation in a reactive oxygen species-dependent manner, and ex vivo-generated human MDSCs also similarly attenuated the proliferative response of autologous T cells to SEB. We propose a role for MDSCs in mitigating excessive tissue injury during TSS.
authors.affiliation: Department of Microbiology and Immunology.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Szabo
authors.affiliation: Department of Microbiology and Immunology.
authors.forename: Ankur
authors.initials: A
authors.lastname: Goswami
authors.affiliation: Department of Microbiology and Immunology.
authors.forename: Arash
authors.initials: A
authors.lastname: Memarnejadian
authors.affiliation: Department of Medical Biophysics Robarts Research Institute.
authors.forename: Christiane L
authors.initials: CL
authors.lastname: Mallett
authors.affiliation: Department of Medical Biophysics Robarts Research Institute.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Foster
authors.affiliation: Department of Microbiology and Immunology Centre for Human Immunology Lawson Health Research Institute, London, Canada.
authors.forename: John K
authors.initials: JK
authors.lastname: McCormick
authors.affiliation: Department of Microbiology and Immunology Centre for Human Immunology Division of Clinical Immunology and Allergy, Department of Medicine, Western University Lawson Health Research Institute, London, Canada.
authors.forename: S M Mansour
authors.initials: SM
authors.lastname: Haeryfar
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D008099:Liver / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*
chemical_list: D039481:CD11b Antigen; D004768:Enterotoxins; D015804:HLA-DR4 Antigen; C509295:ITGAM protein, human; D017382:Reactive Oxygen Species; D018089:Superantigens; C031818:enterotoxin B, staphylococcal
keywords: Staphylococcus aureus; immunosuppression; inflammation; liver; myeloid-derived suppressor cells; staphylococcal enterotoxin B; superantigen