title: Interleukin-17A (IL-17A) and IL-17F Are Critical for Antimicrobial Peptide Production and Clearance of Staphylococcus aureus Nasal Colonization.
abstract: 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.
authors.affiliation: 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.
authors.forename: Nathan K
authors.initials: NK
authors.lastname: Archer
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Nithin D
authors.initials: ND
authors.lastname: Adappa
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: James N
authors.initials: JN
authors.lastname: Palmer
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.|Surgical Service, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.|Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
authors.forename: Noam A
authors.initials: NA
authors.lastname: Cohen
authors.affiliation: Department of Microbial Pathogenesis, Dental School, University of Maryland-Baltimore, Baltimore, Maryland, USA.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Harro
authors.affiliation: Department of Dermatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Dermatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
authors.affiliation: Department of Microbial Pathogenesis, Dental School, University of Maryland-Baltimore, Baltimore, Maryland, USA MShirtliff@umaryland.edu.|Department of Microbiology and Immunology, School of Medicine, University of Maryland-Baltimore, Baltimore, Maryland, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Shirtliff
mesh_terms: D000328:Adult; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D002353:Carrier State / Q000276:immunology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009666:Nose / Q000382:microbiology*; D013211:Staphylococcus aureus; D015854:Up-Regulation; D023083:beta-Defensins
chemical_list: D023181:Antimicrobial Cationic Peptides; D020381:Interleukin-17; D023083:beta-Defensins; C540070:beta-defensin 3, mouse