| First Author | Barin JG | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 9 | Pages | 2337-52 |
| PubMed ID | 27470712 | Mgi Jnum | J:235437 |
| Mgi Id | MGI:5796408 | Doi | 10.1016/j.ajpath.2016.07.001 |
| Citation | Barin JG, et al. (2016) Collaborative Interferon-gamma and Interleukin-17 Signaling Protects the Oral Mucosa from Staphylococcus aureus. Am J Pathol 186(9):2337-52 |
| abstractText | 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)-gamma (IFNgammaRI), beginning at 6 to 8 weeks of age. IFNgammaRI(-/-)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-gamma 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-gamma, acting through neutrophils and macrophages, respectively, in native mucocutaneous host defenses to S. aureus. |
