Archer Nathan K, Adappa Nithin D, Palmer James N, Cohen Noam A, Harro Jan M, Lee Steven K, Miller Lloyd S, Shirtliff Mark E
Department of Microbial Pathogenesis, Dental School, University of Maryland-Baltimore, Baltimore, Maryland, USA.
Graduate Program in Life Sciences, Molecular Microbiology and Immunology Program, University of Maryland-Baltimore, Baltimore, Maryland, USA.
Infect Immun. 2016 Nov 18;84(12):3575-3583. doi: 10.1128/IAI.00596-16. Print 2016 Dec.
Approximately 20% of the population is persistently colonized by Staphylococcus aureus in the nares. Th17-like immune responses mediated by the interleukin-17 (IL-17) family of cytokines and neutrophils are becoming recognized as relevant host defense mechanisms for resolution of S. aureus mucocutaneous infections. Since antimicrobial peptides are regulated by the IL-17 cytokines, we sought to determine the role of IL-17 cytokines in production of antimicrobial peptides in a murine model of S. aureus nasal carriage. We discovered that nasal tissue supernatants have antistaphylococcal activity, and mice deficient in both IL-17A and IL-17F lost the ability to clear S. aureus nasal colonization. IL-17A was found to be sufficient for nasal mBD-3 production ex vivo and was required for CRAMP, mBD-3, and mBD-14 expression in response to S. aureus colonization in vivo These data were confirmed in a clinical study of nasal secretions in which elevated levels of the human forms of these antimicrobial peptides were found in nasal secretions from healthy human subjects when they were colonized with S. aureus but not in secretions from noncolonized subjects. Together, these data provide evidence for the importance of IL-17A regulation of antimicrobial peptides and IL-17F in the clearance of S. aureus nasal carriage.
约20%的人群鼻腔中持续被金黄色葡萄球菌定植。由白细胞介素-17（IL-17）细胞因子家族和中性粒细胞介导的Th17样免疫反应正被视为解决金黄色葡萄球菌黏膜皮肤感染的相关宿主防御机制。由于抗菌肽受IL-17细胞因子调控，我们试图在金黄色葡萄球菌鼻腔定植的小鼠模型中确定IL-17细胞因子在抗菌肽产生中的作用。我们发现鼻组织上清液具有抗葡萄球菌活性，同时缺乏IL-17A和IL-17F的小鼠失去了清除鼻腔中金黄色葡萄球菌定植的能力。发现IL-17A足以在体外产生鼻内mBD-3，并且在体内对金黄色葡萄球菌定植的反应中，CRAMP、mBD-3和mBD-14的表达需要IL-17A。这些数据在一项鼻分泌物临床研究中得到证实，在该研究中，健康人类受试者鼻腔被金黄色葡萄球菌定植时，其鼻分泌物中这些抗菌肽的人源形式水平升高，而非定植受试者的分泌物中则未升高。总之，这些数据证明了IL-17A对抗菌肽的调节以及IL-17F在清除鼻腔中金黄色葡萄球菌定植方面的重要性。
