Collaborative Interferon-γ and Interleukin-17 Signaling Protects the Oral Mucosa from Staphylococcus aureus

Jobert G. Barin, Monica V. Talor, Julie A. Schaub, Nicola L. Diny, Xuezhou Hou, Matthew Hoyer, Nathan Archer, Elizabeth S. Gebremariam, Meghan Davis, Lloyd S Miller, Noel R. Rose, Daniela Cihakova

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2337-2352
Number of pages16
JournalAmerican Journal of Pathology
Volume186
Issue number9
DOIs
StatePublished - Sep 1 2016

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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