Tim Delemarre1, Gabriele Holtappels1, Natalie De Ruyck1, Nan Zhang1, Hans Nauwynck2, Claus Bachert3, Elien Gevaert1. 1. Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium. 2. Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Ghent University, Ghent, Belgium. 3. Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium; Division of Ear, Nose and Throat Diseases, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden. Electronic address: Claus.Bachert@ugent.be.
Abstract
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with severe type 2 immune reactions in the white population. However, recent findings suggest an additional role for neutrophils in severe type 2 inflammation. OBJECTIVE: This study aimed to characterize the neutrophilic inflammation in CRSwNP and its relation to eosinophilic inflammation in severe type 2 immune reactions. METHODS: The presence and activation of neutrophils and eosinophils was analyzed in CRS without NP and CRSwNP by measuring cell and activation markers via immunohistochemistry, immunofluorescence, Luminex assay, ELISA, UniCAP, fluorescence-activated cell sorting, and PCR. Differential neutrophil migration was assessed via Boyden-chamber assay and neutrophil survival was analyzed via flow cytometry. RESULTS: Both CRS without NP and CRSwNP displayed variable degrees of eosinophilic and neutrophilic inflammation, with a profound neutrophilic infiltration and activation in type 2 CRSwNP, associated with eosinophil extracellular traps cell death and Charcot-Leyden crystals, but independent of IL-17. Neutrophil extracellular traps cell death in CRSwNP was associated with bacterial colonization, however, neutrophils were less prone to undergo neutrophil extracellular traps cell death in the tissue of patients with severe type 2 CRSwNP. Neutrophils did not show increased migration nor survival in the CRSwNP environment in vitro. CONCLUSIONS: This study demonstrated a severe neutrophilic inflammation associated with severe eosinophilic type 2 inflammatory CRSwNP, the role of which needs further study.
BACKGROUND:Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with severe type 2 immune reactions in the white population. However, recent findings suggest an additional role for neutrophils in severe type 2 inflammation. OBJECTIVE: This study aimed to characterize the neutrophilic inflammation in CRSwNP and its relation to eosinophilic inflammation in severe type 2 immune reactions. METHODS: The presence and activation of neutrophils and eosinophils was analyzed in CRS without NP and CRSwNP by measuring cell and activation markers via immunohistochemistry, immunofluorescence, Luminex assay, ELISA, UniCAP, fluorescence-activated cell sorting, and PCR. Differential neutrophil migration was assessed via Boyden-chamber assay and neutrophil survival was analyzed via flow cytometry. RESULTS: Both CRS without NP and CRSwNP displayed variable degrees of eosinophilic and neutrophilic inflammation, with a profound neutrophilic infiltration and activation in type 2 CRSwNP, associated with eosinophil extracellular traps cell death and Charcot-Leyden crystals, but independent of IL-17. Neutrophil extracellular traps cell death in CRSwNP was associated with bacterial colonization, however, neutrophils were less prone to undergo neutrophil extracellular traps cell death in the tissue of patients with severe type 2 CRSwNP. Neutrophils did not show increased migration nor survival in the CRSwNP environment in vitro. CONCLUSIONS: This study demonstrated a severe neutrophilic inflammation associated with severe eosinophilic type 2 inflammatory CRSwNP, the role of which needs further study.
Authors: Atsushi Kato; Anju T Peters; Whitney W Stevens; Robert P Schleimer; Bruce K Tan; Robert C Kern Journal: Allergy Date: 2021-09-15 Impact factor: 14.710
Authors: Julie A Poposki; Aiko I Klingler; Whitney W Stevens; Lydia A Suh; Bruce K Tan; Anju T Peters; Hiam Abdala-Valencia; Leslie C Grammer; Kevin C Welch; Stephanie S Smith; David B Conley; Robert C Kern; Robert P Schleimer; Atsushi Kato Journal: J Allergy Clin Immunol Date: 2021-12-22 Impact factor: 14.290