期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 186, 期 9, 页码 2337-2352出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2016.07.001
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资金
- NIB National Heart, Lung, and Blood Institute [R01HL118183, R01HL113008]
- Gilead Sciences Research Scholars program
- American Autoimmune-Related Diseases Association
- American Heart Association [15PRE25400010]
- Richard J. and Margaret Conn Himelfarb Student Support Fund
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 (IFN gamma RI), beginning at 6 to 8 weeks of age. IFN gamma RI-/- 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.
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