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

Elien Gevaert (UGent) , Nan Zhang (UGent) , Olga Krysko (UGent) , Feng Lan (UGent) , Gabriële Holtappels (UGent) , Natalie De Ruyck (UGent) , Hans Nauwynck (UGent) , Shida Yousefi, Hans-Uwe Simon and Claus Bachert (UGent)
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Abstract
Background: Chronic rhinosinusitis with nasal polyps is characterized by T(H)2-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, polyps, Staphylococcus aureus, eosinophils, epithelial barrier, extracellular eosinophilic traps, CHRONIC RHINOSINUSITIS, DNA TRAPS, NASAL POLYPOSIS, DIFFERENTIATION, ENTEROTOXINS, EXPRESSION, CYTOKINES, DISEASES, PROTEIN

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Chicago
Gevaert, Elien, Nan Zhang, Olga Krysko, Feng Lan, Gabriële Holtappels, Natalie De Ruyck, Hans Nauwynck, Shida Yousefi, Hans-Uwe Simon, and Claus Bachert. 2017. “Extracellular Eosinophilic Traps in Association with Staphylococcus Aureus at the Site of Epithelial Barrier Defects in Patients with Severe Airway Inflammation.” Journal of Allergy and Clinical Immunology 139 (6): 1849–1860.
APA
Gevaert, E., Zhang, N., Krysko, O., Lan, F., Holtappels, G., De Ruyck, N., Nauwynck, H., et al. (2017). Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 139(6), 1849–1860.
Vancouver
1.
Gevaert E, Zhang N, Krysko O, Lan F, Holtappels G, De Ruyck N, et al. Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2017;139(6):1849–60.
MLA
Gevaert, Elien, Nan Zhang, Olga Krysko, et al. “Extracellular Eosinophilic Traps in Association with Staphylococcus Aureus at the Site of Epithelial Barrier Defects in Patients with Severe Airway Inflammation.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 139.6 (2017): 1849–1860. Print.
@article{8506569,
  abstract     = {Background: Chronic rhinosinusitis with nasal polyps is characterized by T(H)2-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 {\textlangle} .05) and periostin (P {\textlangle} .05) tissue levels and colonization with S aureus (P {\textlangle} .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 {\textlangle} .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 {\textlangle} .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.},
  author       = {Gevaert, Elien and Zhang, Nan and Krysko, Olga and Lan, Feng and Holtappels, Gabri{\"e}le and De Ruyck, Natalie and Nauwynck, Hans and Yousefi, Shida and Simon, Hans-Uwe and Bachert, Claus},
  issn         = {0091-6749},
  journal      = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
  keyword      = {Chronic rhinosinusitis,polyps,Staphylococcus aureus,eosinophils,epithelial barrier,extracellular eosinophilic traps,CHRONIC RHINOSINUSITIS,DNA TRAPS,NASAL POLYPOSIS,DIFFERENTIATION,ENTEROTOXINS,EXPRESSION,CYTOKINES,DISEASES,PROTEIN},
  language     = {eng},
  number       = {6},
  pages        = {1849--1860},
  title        = {Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation},
  url          = {http://dx.doi.org/10.1016/j.jaci.2017.01.019},
  volume       = {139},
  year         = {2017},
}

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