- Title
- Mechanical forces suppress antiviral innate immune responses from asthmatic airway epithelial cells following rhinovirus infection
- Creator
- Veerati, Punnam Chander; Reid, Andrew T.; Nichol, Kristy S.; Wark, Peter A. B.; Knight, Darryl A.; Bartlett, Nathan W.; Grainge, Christopher L.
- Relation
- American Journal of Physiology: Lung Cellular and Molecular Physiology Vol. 325, Issue 2, p. L206-L214
- Publisher Link
- http://dx.doi.org/10.1152/ajplung.00074.2022
- Publisher
- American Physiological Society
- Resource Type
- journal article
- Date
- 2023
- Description
- Bronchoconstriction is the main physiological event in asthma, which leads to worsened clinical symptoms and generates mechanical stress within the airways. Virus infection is the primary cause of exacerbations in people with asthma, however, the impact that bronchoconstriction itself on host anti-viral responses and viral replication is currently not well understood. Here we demonstrate how mechanical forces generated during bronchoconstriction may suppress antiviral responses at the airway epithelium without any difference in viral replication. METHODS: Primary bronchial epithelial cells from donors with asthma were differentiated at the air-liquid interface. Differentiated cells were apically compressed (30cm H2O) for 10 minutes every hour for 4 days to mimic bronchoconstriction. Two asthma disease models were developed with the application of compression, either prior to ("poor asthma control model", n=7) or following ("exacerbation model", n=4) rhinovirus (RV) infection. Samples were collected at 0, 24, 48, 72 and 96h post-infection (hpi). Viral RNA, IFN-β and IFN-λ gene expression was measured along with IFN-β, IFN-λ, TGF-β2, IL-6 and IL-8 protein expression. RESULTS: Apical compression significantly suppressed RV induced IFN-β protein from 48hpi and IFN-λ from 72hpi in the poor asthma control model. There was a non-significant reduction of both IFN-β and IFN-λ proteins from 48hpi in the exacerbation model. Despite reductions in antiviral proteins, there was no significant change in viral replication in either model. CONCLUSION: Compressive stress mimicking bronchoconstriction inhibits anti-viral innate immune responses from asthmatic airway epithelial cells when applied prior to RV infection.
- Subject
- antiviral innate immune responses; asthma; bronchoconstriction; mechanical forces; rhinovirus; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1483953
- Identifier
- uon:51239
- Identifier
- ISSN:1522-1504
- Rights
- Copyright © 2023 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0. Published by the American Physiological Society.
- Language
- eng
- Full Text
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