title: Differential induction of innate defense antimicrobial peptides in primary nasal epithelial cells upon stimulation with inflammatory cytokines, Th17 cytokines or bacterial conditioned medium from Staphylococcus aureus isolates.
abstract: To date it is incompletely understood why half of the human population is intrinsically resistant to Staphylococcus aureus colonization whereas the other half is intermittently or permanently colonized. Nasal colonization represents the primary niche for S. aureus. We therefore investigated whether primary nasal epithelial cells (HNEC) express antimicrobial peptides (AMPs) upon stimulation by inflammatory cytokines or bacterial conditioned medium (BCM) of different colonizing and invasive staphylococci. Stimulation with classical cytokines (IL-1β, TNF-α, IFN-γ) potently induced hBD-3 and RNase7 in HNEC. Th17 cytokines (IL-17A, IL-17F, IL-22) yielded comparably weak hBD-3 and RNase7 induction and no synergistic effects with classical cytokines. BCM of S. aureus and Staphylococcus epidermidis isolates moderately induced hBD3 and RNase7 mRNA expression without significant differences when comparing colonizing vs. invasive isolates. Our results indicate that HNEC contribute to the innate defense by secretion of an AMP-containing chemical defense shield along the nasal mucosa i.e. within the primary colonization niche of S. aureus. Further studies are needed to investigate whether a deficient AMP expression in the nasal mucosa may be related to different S. aureus carrier states. AMPs or AMP-inducing agents may be promising candidates for future topical decolonization regimens that aim to prevent invasive S. aureus infections.
authors.affiliation: Division of Infectious Diseases, Department of Medicine II, University Medical Center Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany; Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104, Freiburg, Germany. Electronic address: christine.burgey@gmail.com.
authors.forename: Christine
authors.initials: C
authors.lastname: Burgey
authors.affiliation: Division of Infectious Diseases, Department of Medicine II, University Medical Center Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.
authors.forename: Winfried V
authors.initials: WV
authors.lastname: Kern
authors.affiliation: Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104, Freiburg, Germany; BIOSS - Centre for Biological Signalling Studies, Schänzlestraβe 18, Albert-Ludwigs-University Freiburg, 79104, Freiburg, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Römer
authors.affiliation: Division of Infectious Diseases, Department of Medicine II, University Medical Center Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.
authors.forename: Siegbert
authors.initials: S
authors.lastname: Rieg
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D002353:Carrier State / Q000382:microbiology; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D009297:Nasal Mucosa / Q000276:immunology* / Q000382:microbiology*; D012260:Ribonucleases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D013212:Staphylococcus epidermidis / Q000378:metabolism; D015854:Up-Regulation; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D017077:Culture Media, Conditioned; D016207:Cytokines; C422950:DEFB103A protein, human; D023083:beta-Defensins; D012260:Ribonucleases; C470000:Ribonuclease 7; D054804:Cathelicidins
keywords: Bacteremia; Colonization; Host-pathogen interaction; Infection; Nasal carriage; Staphylococcus aureus