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

Gevaert, Elien; Zhang, Nan; Krysko, Olga; Lan, Feng; Holtappels, Gabriële; De Ruyck, Natalie; Nauwynck, Hans; Yousefi, Shida; Simon, Hans-Uwe; Bachert, Claus (2017). Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in severe airway inflammation. The Journal of allergy and clinical immunology, 139(6), 1849-1860.e6. Elsevier 10.1016/j.jaci.2017.01.019

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BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a Th2-biased eosinophilic inflammation. Eosinophils have been shown to generate so-called extracellular eosinophilic traps (EETs) under similar pathological 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, using immunofluorescent staining and PNA-fish assay respectively. An ex vivo human mucosal disease tissue model was used for artificial infection with S. aureus. Cell markers were analyzed using immunohistochemistry, luminex Multiplex assay, ELISA, PCR, immunobloting and linked to the presence of EETs. RESULTS About 8.8 ± 4.8 % of the infiltrating eosinophils exhibited EETs in patient's nasal polyp tissues. The formation of EETs was associated with increased IL-5 (p < 0.05) and periostin (p < 0.05) tissue levels, and colonization with S. aureus (p < 0.05). Using an ex vivo human mucosal disease tissue model, EET formation was induced (4.2 ± 0.9 fold) upon exposure to S. aureus, but not to S. epidermidis. Eosinophils were shown to migrate (p < 0.01) towards S. aureus and entrap the bacteria both inside and outside the mucosal tissue. Blocking NAPDH oxidase activity, led to a complete inhibition (p < 0.05) of EET formation by S. aureus. CONCLUSION Eosinophils are likely to be specifically recruited to and form EETs at sites of airway epithelial damage to protect the host from infections with S. aureus and possibly other microorganisms in CRSwNP.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Yousefi, Shida and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1097-6825

Publisher:

Elsevier

Language:

English

Submitter:

Jana Berger

Date Deposited:

11 Sep 2017 09:41

Last Modified:

01 Jul 2018 02:30

Publisher DOI:

10.1016/j.jaci.2017.01.019

PubMed ID:

28216437

BORIS DOI:

10.7892/boris.96298

URI:

https://boris.unibe.ch/id/eprint/96298

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