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 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.
Abstract
The airway epithelial pro-inflammatory and anti-viral response to a viral stimulus differs with the phenotype and severity of asthma, indicating differences in immune drivers of exacerbations https://bit.ly/3DhTVWw
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.00194-2022
Author contributions: All authors contributed to the design of the study, patient sampling, laboratory analysis, statistical analysis and development of the manuscript.
Conflict of interest: All authors declare no potential conflicts of interest in relation to the present study. C. Porsbjerg declares having received honoraria as a speaker and consultant, and unrestricted research grants from AZ, GSK, Novartis, Sanofi, TEVA, Chiesi and Pharmaxis. A. Sverrild declares having received honoraria as a speaker and consultant, and unrestricted research grants from AZ, Novartis, Sanofi and Chiesi.
Support statement: The project was funded by grants from the Swedish Medical Research Council, grant number 2020-00922_VR and 2017-00806_VR, as well as the Swedish Heart and Lung Foundation (20180207_HLF), Lundbeck Foundation, Capital region of Copenhagen Foundation and the Interreg foundation. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received August 25, 2021.
- Accepted November 24, 2021.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
LIBRARY USERS
Log in through your institution
Purchase access
