Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic
(2022) In The European respiratory journal 60(1).- Abstract
BACKGROUND: Asthma is characterised by an aggravated immune response to respiratory viral infections. This phenomenon is a clinically well-recognised driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to viruses is unclear. OBJECTIVES: To describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation. METHODS: In the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 14 (28%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and... (More)
BACKGROUND: Asthma is characterised by an aggravated immune response to respiratory viral infections. This phenomenon is a clinically well-recognised driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to viruses is unclear. OBJECTIVES: To describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation. METHODS: In the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 14 (28%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and stimulated with the viral replication mimic poly (I:C) (Toll-like receptor (TLR)3 agonist) in vitro. The expression of TLR3-induced pro-inflammatory and antiviral responses of BECs were analysed using reverse transcriptase quantitative PCR and multiplex ELISA and compared across asthma phenotypes and severity of disease. RESULTS: Patients with atopic asthma had increased induction of interleukin (IL)-4, interferon (IFN)-β, IL-6, tumour necrosis factor-α, and IL-1β after poly (I:C) stimulation compared to non-atopic patients, whereas in patients with eosinophilic asthma only IL-6 and IL-8 induction was higher than in non-eosinophilic asthma. Patients with severe asthma displayed a decreased antiviral IFN-β, and increased expression of IL-8, most pronounced in atopic and eosinophilic asthmatics. Furthermore, induction of IL-33 in response to poly (I:C) was increased in severe atopic and in severe eosinophilic asthma, but thymic stromal lymphopoietin only in severe eosinophilic asthma. CONCLUSIONS: The bronchial epithelial immune response to a viral mimic stimulation differs between asthma phenotypes and severities, which may be important to consider when targeting novel asthma treatments.
(Less)
- author
- organization
- publishing date
- 2022-07-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The European respiratory journal
- volume
- 60
- issue
- 1
- publisher
- European Respiratory Society
- external identifiers
-
- scopus:85135375914
- pmid:34916261
- ISSN
- 1399-3003
- DOI
- 10.1183/13993003.02333-2021
- language
- English
- LU publication?
- yes
- id
- d6b2a6bd-e9e8-4a7f-b5c8-1c1fb09257d1
- date added to LUP
- 2022-10-28 14:14:56
- date last changed
- 2024-12-13 16:45:00
@article{d6b2a6bd-e9e8-4a7f-b5c8-1c1fb09257d1,
abstract = {{<p>BACKGROUND: Asthma is characterised by an aggravated immune response to respiratory viral infections. This phenomenon is a clinically well-recognised driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to viruses is unclear. OBJECTIVES: To describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation. METHODS: In the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 14 (28%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and stimulated with the viral replication mimic poly (I:C) (Toll-like receptor (TLR)3 agonist) in vitro. The expression of TLR3-induced pro-inflammatory and antiviral responses of BECs were analysed using reverse transcriptase quantitative PCR and multiplex ELISA and compared across asthma phenotypes and severity of disease. RESULTS: Patients with atopic asthma had increased induction of interleukin (IL)-4, interferon (IFN)-β, IL-6, tumour necrosis factor-α, and IL-1β after poly (I:C) stimulation compared to non-atopic patients, whereas in patients with eosinophilic asthma only IL-6 and IL-8 induction was higher than in non-eosinophilic asthma. Patients with severe asthma displayed a decreased antiviral IFN-β, and increased expression of IL-8, most pronounced in atopic and eosinophilic asthmatics. Furthermore, induction of IL-33 in response to poly (I:C) was increased in severe atopic and in severe eosinophilic asthma, but thymic stromal lymphopoietin only in severe eosinophilic asthma. CONCLUSIONS: The bronchial epithelial immune response to a viral mimic stimulation differs between asthma phenotypes and severities, which may be important to consider when targeting novel asthma treatments.</p>}},
author = {{Porsbjerg, Celeste and Nieto-Fontarigo, Juan Jose and Cerps, Samuel and Ramu, Sangheeta and Menzel, Mandy and Hvidtfeldt, Morten and Silberbrandt, Alexander and Frøssing, Laurits and Klein, Ditte and Sverrild, Asger and Uller, Lena}},
issn = {{1399-3003}},
language = {{eng}},
month = {{07}},
number = {{1}},
publisher = {{European Respiratory Society}},
series = {{The European respiratory journal}},
title = {{Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic}},
url = {{http://dx.doi.org/10.1183/13993003.02333-2021}},
doi = {{10.1183/13993003.02333-2021}},
volume = {{60}},
year = {{2022}},
}