TY - JOUR
T1 - Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes
AU - Ghanizada, Muzhda
AU - Malm Tillgren, Sofia
AU - Praeger-Jahnsen, Louis
AU - Said, Nihaya Mahmoud
AU - Ditlev, Sisse
AU - Frost Andreassen, Helle
AU - Dyhre-Petersen, Nanna
AU - Cerps, Samuel
AU - Sverrild, Asger
AU - Porsbjerg, Celeste
AU - Uller, Lena
AU - Lapperre, Therese
AU - Menzel, Mandy
N1 - © 2025 Ghanizada, Malm Tillgren, Praeger-Jahnsen, Said, Ditlev, Frost Andreassen, Dyhre-Petersen, Cerps, Sverrild, Porsbjerg, Uller, Lapperre and Menzel.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
U2 - 10.3389/falgy.2025.1605109
DO - 10.3389/falgy.2025.1605109
M3 - Journal article
C2 - 40599681
SN - 2673-6101
VL - 6
JO - Frontiers in allergy
JF - Frontiers in allergy
M1 - 1605109
ER -