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Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes

Ghanizada, Muzhda ; Malm Tillgren, Sofia LU orcid ; Praeger-Jahnsen, Louis ; Said, Nihaya Mahmoud ; Ditlev, Sisse ; Frost Andreassen, Helle ; Dyhre-Petersen, Nanna ; Cerps, Samuel LU ; Sverrild, Asger and Porsbjerg, Celeste , et al. (2025) In Frontiers in Allergy 6.
Abstract

Background: Azithromycin (AZM) effectively reduces asthma exacerbations and enhances bronchial epithelial cell (BEC) antiviral immunity in vitro. However, its clinical impact on different asthma phenotypes is not fully elucidated and differences in treatment response to AZM may be attributable to differences in immune activation to rhinovirus (RV) infection in different inflammatory asthma phenotypes. Objectives: To explore bronchial epithelial antiviral properties in response to in vitro AZM treatment in eosinophilic and non-eosinophilic as well as atopic and non-atopic asthma phenotypes, and to investigate the effects of AZM on the release of RV-induced alarmins and pro-inflammatory cytokines in these asthma phenotypes. Methods: In... (More)

Background: Azithromycin (AZM) effectively reduces asthma exacerbations and enhances bronchial epithelial cell (BEC) antiviral immunity in vitro. However, its clinical impact on different asthma phenotypes is not fully elucidated and differences in treatment response to AZM may be attributable to differences in immune activation to rhinovirus (RV) infection in different inflammatory asthma phenotypes. Objectives: To explore bronchial epithelial antiviral properties in response to in vitro AZM treatment in eosinophilic and non-eosinophilic as well as atopic and non-atopic asthma phenotypes, and to investigate the effects of AZM on the release of RV-induced alarmins and pro-inflammatory cytokines in these asthma phenotypes. Methods: In this cross-sectional study, we have collected BECs from patients with moderate-to-severe asthma (n = 20). The cells were pre-treated with or without 10 µM AZM 24 h before infection with 0.05 MOI RV. Release of IFN-β, IFN-λ, alarmins and pro-inflammatory cytokines were measured 48 h after infection by Mesoscale Discovery (S-plex and U-plex) and then compared across asthma phenotypes, based on blood eosinophils and atopy status. Results: AZM significantly enhanced IFN-β and IFN-λ protein release in response to RV infection both in eosinophilic and in non-eosinophilic asthma as well as in non-atopic asthma. A less pronounced IFN-β and IFN-λ protein release was also observed in the atopic group. AZM's interferon-inducing effect was, however, largely similar regardless of blood eosinophil count and atopy status. Additionally, AZM prompted the release of TSLP and IL-6 in the non-eosinophilic group only. Conclusions: Our data suggest that in vitro, AZM works primarily by improving bronchial epithelial antiviral resistance by increasing interferons independent of eosinophilia and atopy status, highlighting the broad applicability of AZM in modulating antiviral immunity in asthma as well as the need for identifying predictors of AZM response beyond inflammatory phenotypes.

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Contribution to journal
publication status
published
subject
keywords
antiviral immunity, asthma exacerbation, atopy, azithromycin (AZM), bronchial epithelial cell, rhinovirus
in
Frontiers in Allergy
volume
6
article number
1605109
publisher
Frontiers Media S. A.
external identifiers
  • scopus:105009728468
  • pmid:40599681
ISSN
2673-6101
DOI
10.3389/falgy.2025.1605109
language
English
LU publication?
yes
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Publisher Copyright: 2025 Ghanizada, Malm Tillgren, Praeger-Jahnsen, Said, Ditlev, Frost Andreassen, Dyhre-Petersen, Cerps, Sverrild, Porsbjerg, Uller, Lapperre and Menzel.
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c24e813c-a4a1-4247-bfac-b359040b0683
date added to LUP
2026-01-21 13:05:36
date last changed
2026-01-22 03:00:02
@article{c24e813c-a4a1-4247-bfac-b359040b0683,
  abstract     = {{<p>Background: Azithromycin (AZM) effectively reduces asthma exacerbations and enhances bronchial epithelial cell (BEC) antiviral immunity in vitro. However, its clinical impact on different asthma phenotypes is not fully elucidated and differences in treatment response to AZM may be attributable to differences in immune activation to rhinovirus (RV) infection in different inflammatory asthma phenotypes. Objectives: To explore bronchial epithelial antiviral properties in response to in vitro AZM treatment in eosinophilic and non-eosinophilic as well as atopic and non-atopic asthma phenotypes, and to investigate the effects of AZM on the release of RV-induced alarmins and pro-inflammatory cytokines in these asthma phenotypes. Methods: In this cross-sectional study, we have collected BECs from patients with moderate-to-severe asthma (n = 20). The cells were pre-treated with or without 10 µM AZM 24 h before infection with 0.05 MOI RV. Release of IFN-β, IFN-λ, alarmins and pro-inflammatory cytokines were measured 48 h after infection by Mesoscale Discovery (S-plex and U-plex) and then compared across asthma phenotypes, based on blood eosinophils and atopy status. Results: AZM significantly enhanced IFN-β and IFN-λ protein release in response to RV infection both in eosinophilic and in non-eosinophilic asthma as well as in non-atopic asthma. A less pronounced IFN-β and IFN-λ protein release was also observed in the atopic group. AZM's interferon-inducing effect was, however, largely similar regardless of blood eosinophil count and atopy status. Additionally, AZM prompted the release of TSLP and IL-6 in the non-eosinophilic group only. Conclusions: Our data suggest that in vitro, AZM works primarily by improving bronchial epithelial antiviral resistance by increasing interferons independent of eosinophilia and atopy status, highlighting the broad applicability of AZM in modulating antiviral immunity in asthma as well as the need for identifying predictors of AZM response beyond inflammatory phenotypes.</p>}},
  author       = {{Ghanizada, Muzhda and Malm Tillgren, Sofia and Praeger-Jahnsen, Louis and Said, Nihaya Mahmoud and Ditlev, Sisse and Frost Andreassen, Helle and Dyhre-Petersen, Nanna and Cerps, Samuel and Sverrild, Asger and Porsbjerg, Celeste and Uller, Lena and Lapperre, Therese and Menzel, Mandy}},
  issn         = {{2673-6101}},
  keywords     = {{antiviral immunity; asthma exacerbation; atopy; azithromycin (AZM); bronchial epithelial cell; rhinovirus}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Allergy}},
  title        = {{Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes}},
  url          = {{http://dx.doi.org/10.3389/falgy.2025.1605109}},
  doi          = {{10.3389/falgy.2025.1605109}},
  volume       = {{6}},
  year         = {{2025}},
}