Elien Gevaert1, Nan Zhang1, Olga Krysko1, Feng Lan1, Gabriële Holtappels1, Natalie De Ruyck1, Hans Nauwynck2, Shida Yousefi3, Hans-Uwe Simon3, Claus Bachert4. 1. Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium. 2. Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium. 3. Institute of Pharmacology, University of Bern, Bern, Switzerland. 4. 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.
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.
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 humanmucosal 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 humanmucosal 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.
Authors: Hans-Uwe Simon; Shida Yousefi; Nina Germic; Isabelle C Arnold; Angela Haczku; Alexander V Karaulov; Dagmar Simon; Helene F Rosenberg Journal: Int Arch Allergy Immunol Date: 2019-11-29 Impact factor: 2.749