Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation

J Allergy Clin Immunol. 2017 Jun;139(6):1849-1860.e6. doi: 10.1016/j.jaci.2017.01.019. Epub 2017 Feb 17.

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.

Conclusion: 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.

Keywords: Chronic rhinosinusitis; Staphylococcus aureus; eosinophils; epithelial barrier; extracellular eosinophilic traps; polyps.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chronic Disease
  • Eosinophils / immunology
  • Extracellular Traps / immunology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nasal Mucosa* / immunology
  • Nasal Mucosa* / microbiology
  • Nasal Polyps* / immunology
  • Nasal Polyps* / microbiology
  • Rhinitis* / immunology
  • Rhinitis* / microbiology
  • Sinusitis* / immunology
  • Sinusitis* / microbiology
  • Staphylococcal Infections* / immunology
  • Staphylococcus aureus*
  • Young Adult