title: Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation.
abstract: BACKGROUND
  Chronic rhinosinusitis with nasal polyps is characterized by TH2-biased eosinophilic inflammation. Eosinophils have been shown to generate so-called extracellular eosinophilic traps (EETs) under similar pathologic conditions.
  
  
  OBJECTIVE
  Our aim was to investigate a possible link between EET formation and the presence of Staphylococcus aureus, an organism frequently colonizing the upper airways, at the human mucosal site of the disease.
  
  
  METHODS
  Tissue slides were investigated for the presence of EETs and S aureus by using immunofluorescent staining and the PNA-Fish assay, respectively. An ex vivo human mucosal disease tissue model was used for artificial infection with S aureus. Cell markers were analyzed by using immunohistochemistry, the Luminex Multiplex assay, ELISA, PCR, and immunoblotting and linked to the presence of EETs.
  
  
  RESULTS
  About 8.8% ± 4.8% of the infiltrating eosinophils exhibited EETs in patients' nasal polyp tissues. Formation of EETs was associated with increased IL-5 (P < .05) and periostin (P < .05) tissue levels and colonization with S aureus (P < .05). By using an ex vivo human mucosal disease tissue model, EET formation was induced (4.2 ± 0.9-fold) on exposure to S aureus but not Staphylococcus epidermidis. Eosinophils were shown to migrate (P < .01) toward S aureus and entrap the bacteria both inside and outside the mucosal tissue. Blocking NAPDH oxidase activity led to a complete inhibition (P < .05) of EET formation by S aureus.
  
  
  CONCLUSIONS
  Eosinophils are likely to be specifically recruited to S aureus and possibly other microorganisms and form EETs at sites of airway epithelial damage to protect the host from infections in patients with chronic rhinosinusitis with nasal polyps.
authors.affiliation: Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium.
authors.forename: Elien
authors.initials: E
authors.lastname: Gevaert
authors.affiliation: Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium.
authors.forename: Olga
authors.initials: O
authors.lastname: Krysko
authors.affiliation: Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium.
authors.forename: Feng
authors.initials: F
authors.lastname: Lan
authors.affiliation: Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium.
authors.forename: Gabriële
authors.initials: G
authors.lastname: Holtappels
authors.affiliation: Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium.
authors.forename: Natalie
authors.initials: N
authors.lastname: De Ruyck
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Nauwynck
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Shida
authors.initials: S
authors.lastname: Yousefi
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
authors.affiliation: Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium; Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden. Electronic address: Claus.Bachert@ugent.be.
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D004804:Eosinophils / Q000276:immunology; D065206:Extracellular Traps / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000382:microbiology; D009298:Nasal Polyps / Q000276:immunology / Q000382:microbiology; D012220:Rhinitis / Q000276:immunology / Q000382:microbiology; D012852:Sinusitis / Q000276:immunology / Q000382:microbiology; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus; D055815:Young Adult
keywords: Chronic rhinosinusitis; Staphylococcus aureus; eosinophils; epithelial barrier; extracellular eosinophilic traps; polyps