title: Collaborative Interferon-γ and Interleukin-17 Signaling Protects the Oral Mucosa from Staphylococcus aureus.
abstract: Infections with Staphylococcus aureus are a continuing and growing problem in community and hospital settings. Preclinical animal modeling of S. aureus relies on experimental infection, which carries some limitations. We describe here a novel, spontaneous model of oral staphylococcal infection in double knockout mice, deficient in the receptors for IL-17 (IL-17RA) and interferon (IFN)-γ (IFNγRI), beginning at 6 to 8 weeks of age. IFNγRI(-/-)IL17RA(-/-) (GRAKO) mice developed progressive oral abscesses. Cytometric methods revealed extensive neutrophilic infiltration of oral tissues in GRAKO mice; further investigation evidenced that IL-17 predominated neutrophil defects in these mice. To investigate the contribution of IFN-γ signaling to this native host defense to S. aureus, we observed perturbations of monocyte recruitment and macrophage differentiation in the oral tissues of GRAKO mice, and CXCL9/chemokine ligand receptor (CXCR)3-driven recruitment of T-cell oral tissues and draining lymph nodes. To address the former finding, we depleted macrophages and monocytes in vivo from IL17RA(-/-) mice using liposomes loaded with clodronate. This treatment elicited oral abscesses, recapitulating the phenotype of GRAKO mice. From these findings, we propose novel collaborative functions of IL-17 and IFN-γ, acting through neutrophils and macrophages, respectively, in native mucocutaneous host defenses to S. aureus.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jobert G
authors.initials: JG
authors.lastname: Barin
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Monica V
authors.initials: MV
authors.lastname: Talor
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schaub
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology & Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Diny
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology & Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Xuezhou
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hoyer
authors.affiliation: Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Nathan K
authors.initials: NK
authors.lastname: Archer
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Gebremariam
authors.affiliation: Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Meghan F
authors.initials: MF
authors.lastname: Davis
authors.affiliation: Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; W. Harry Feinstone Department of Molecular Microbiology & Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Noel R
authors.initials: NR
authors.lastname: Rose
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; W. Harry Feinstone Department of Molecular Microbiology & Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Electronic address: dcihako1@jhmi.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Čiháková
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000276:immunology* / Q000382:microbiology*; D015398:Signal Transduction / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus
chemical_list: D020381:Interleukin-17; D007371:Interferon-gamma