Interleukin-17A (IL-17A) and IL-17F Are Critical for Antimicrobial Peptide Production and Clearance of Staphylococcus aureus Nasal Colonization

被引:52
作者
Archer, Nathan K. [1 ,2 ,3 ]
Adappa, Nithin D. [4 ]
Palmer, James N. [4 ]
Cohen, Noam A. [4 ,5 ,6 ]
Harro, Jan M. [1 ]
Lee, Steven K. [3 ]
Miller, Lloyd S. [3 ]
Shirtliff, Mark E. [1 ,7 ]
机构
[1] Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA
[2] Univ Maryland, Mol Microbiol & Immunol Program, Grad Program Life Sci, Baltimore, MD 21201 USA
[3] Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA
[4] Univ Penn, Sch Med, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA
[5] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA
[6] Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA
[7] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA
关键词
BETA-DEFENSIN; 3; HUMAN BETA-DEFENSIN-3; INNATE IMMUNITY; MOUSE BETA-DEFENSIN-14; BACTERIAL-INFECTION; HUMAN KERATINOCYTES; INDUCIBLE PEPTIDE; HUMAN LUNG; EXPRESSION; SKIN;
D O I
10.1128/IAI.00596-16
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:3575 / 3583
页数:9
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