[HTML][HTML] Collaborative interferon-γ and interleukin-17 signaling protects the oral mucosa from Staphylococcus aureus

JG Barin, MV Talor, JA Schaub, NL Diny, X Hou… - The American journal of …, 2016 - Elsevier
JG Barin, MV Talor, JA Schaub, NL Diny, X Hou, M Hoyer, NK Archer, ES Gebremariam…
The American journal of pathology, 2016Elsevier
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 …
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.
Elsevier