Association between mucosal barrier disruption by Pseudomonas aeruginosa exoproteins and asthma in patients with chronic rhinosinusitis

Background Chronic rhinosinusitis (CRS) is a common chronic respiratory condition, frequently associated with asthma and affecting the majority of cystic fibrosis (CF) patients. Pseudomonas aeruginosa infections and biofilms have been implicated in recalcitrant CRS. One of the mechanisms of action f...

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Bibliographic Details
Published in:Allergy (Copenhagen) 2021-11, Vol.76 (11), p.3459-3469
Main Authors: Tuli, Jannatul Ferdoush, Ramezanpour, Mahnaz, Cooksley, Clare, Psaltis, Alkis James, Wormald, Peter‐John, Vreugde, Sarah
Format: Article
Language:English
Subjects:
Asthma
Biofilms
Cell viability
chronic rhinosinusitis
Clinical isolates
Cystic fibrosis
Cytotoxicity
Electrical resistivity
Enzyme-linked immunosorbent assay
Epithelial cells
exoproteins
Immunofluorescence
Inflammation
Mucosa
mucosal barrier
Patients
Permeability
Pseudomonas aeruginosa
Rhinitis
Rhinosinusitis
Sinusitis
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Summary:Background Chronic rhinosinusitis (CRS) is a common chronic respiratory condition, frequently associated with asthma and affecting the majority of cystic fibrosis (CF) patients. Pseudomonas aeruginosa infections and biofilms have been implicated in recalcitrant CRS. One of the mechanisms of action for bacteria in CRS and CF is mucosal barrier disruption by secreted products that contribute to the inflammation. However, the role of biofilm and planktonic forms of P. aeruginosa in this process is not known. The aim is to determine the effect of P. aeruginosa exoproteins isolated from CF and non‐CF CRS patients on the mucosal barrier. Methods Exoproteins from 40 P. aeruginosa isolates were collected in planktonic and biofilm forms and applied to air‐liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs). Mucosal barrier integrity was evaluated by transepithelial electrical resistance (TEER), passage of FITC‐dextrans and immunofluorescence of tight junction proteins. Cytotoxicity assays were performed to measure cell viability, and IL‐6 ELISA was carried out to evaluate pro‐inflammatory effects. Results Planktonic exoproteins from 20/40 (50%) clinical isolates had a significant detrimental effect on the barrier and significantly increased IL‐6 production. Barrier disruption was characterized by a reduced TEER, increased permeability of FITC‐dextrans and discontinuous immunolocalization of tight junction proteins and was significantly more prevalent in isolates harvested from patients with comorbid asthma (P 
ISSN:0105-4538
1398-9995
DOI:10.1111/all.14959