Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes
BackgroundAzithromycin (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 diff...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Allergy |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/falgy.2025.1605109/full |
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| author | Muzhda Ghanizada Sofia Malm Tillgren Louis Praeger-Jahnsen Nihaya Mahmoud Said Sisse Ditlev Helle Frost Andreassen Nanna Dyhre-Petersen Samuel Cerps Asger Sverrild Celeste Porsbjerg Lena Uller Therese Lapperre Therese Lapperre Therese Lapperre Mandy Menzel |
| author_facet | Muzhda Ghanizada Sofia Malm Tillgren Louis Praeger-Jahnsen Nihaya Mahmoud Said Sisse Ditlev Helle Frost Andreassen Nanna Dyhre-Petersen Samuel Cerps Asger Sverrild Celeste Porsbjerg Lena Uller Therese Lapperre Therese Lapperre Therese Lapperre Mandy Menzel |
| author_sort | Muzhda Ghanizada |
| collection | DOAJ |
| description | BackgroundAzithromycin (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.ObjectivesTo 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.MethodsIn 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.ResultsAZM 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.ConclusionsOur 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. |
| format | Article |
| id | doaj-art-902206a095ef4cf3aa71e20ec22357dd |
| institution | Kabale University |
| issn | 2673-6101 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Allergy |
| spelling | doaj-art-902206a095ef4cf3aa71e20ec22357dd2025-08-20T03:31:21ZengFrontiers Media S.A.Frontiers in Allergy2673-61012025-06-01610.3389/falgy.2025.16051091605109Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypesMuzhda Ghanizada0Sofia Malm Tillgren1Louis Praeger-Jahnsen2Nihaya Mahmoud Said3Sisse Ditlev4Helle Frost Andreassen5Nanna Dyhre-Petersen6Samuel Cerps7Asger Sverrild8Celeste Porsbjerg9Lena Uller10Therese Lapperre11Therese Lapperre12Therese Lapperre13Mandy Menzel14Respiratory Research Unit, Department of Respiratory and Infectious Diseases, Bispebjerg Hospital, Copenhagen, DenmarkUnit of Respiratory Immunopharmacology, Department of Experimental Medical Science, Lund University, Lund, SwedenCopenhagen Centre for Translational Research, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, DenmarkRespiratory Research Unit, Department of Respiratory and Infectious Diseases, Bispebjerg Hospital, Copenhagen, DenmarkCopenhagen Centre for Translational Research, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, DenmarkRespiratory Research Unit, Department of Respiratory and Infectious Diseases, Bispebjerg Hospital, Copenhagen, DenmarkRespiratory Research Unit, Department of Respiratory and Infectious Diseases, Bispebjerg Hospital, Copenhagen, DenmarkUnit of Respiratory Immunopharmacology, Department of Experimental Medical Science, Lund University, Lund, SwedenRespiratory Research Unit, Department of Respiratory and Infectious Diseases, Bispebjerg Hospital, Copenhagen, DenmarkRespiratory Research Unit, Department of Respiratory and Infectious Diseases, Bispebjerg Hospital, Copenhagen, DenmarkUnit of Respiratory Immunopharmacology, Department of Experimental Medical Science, Lund University, Lund, SwedenRespiratory Research Unit, Department of Respiratory and Infectious Diseases, Bispebjerg Hospital, Copenhagen, DenmarkDepartment of Respiratory Medicine, Antwerp University Hospital, Antwerp, BelgiumLaboratory of Experimental Medicine and Paediatrics, University of Antwerp, Wilrijk, BelgiumUnit of Respiratory Immunopharmacology, Department of Experimental Medical Science, Lund University, Lund, SwedenBackgroundAzithromycin (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.ObjectivesTo 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.MethodsIn 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.ResultsAZM 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.ConclusionsOur 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.https://www.frontiersin.org/articles/10.3389/falgy.2025.1605109/fullasthma exacerbationantiviral immunityatopyrhinovirusbronchial epithelial cellazithromycin (AZM) |
| spellingShingle | Muzhda Ghanizada Sofia Malm Tillgren Louis Praeger-Jahnsen Nihaya Mahmoud Said Sisse Ditlev Helle Frost Andreassen Nanna Dyhre-Petersen Samuel Cerps Asger Sverrild Celeste Porsbjerg Lena Uller Therese Lapperre Therese Lapperre Therese Lapperre Mandy Menzel Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes Frontiers in Allergy asthma exacerbation antiviral immunity atopy rhinovirus bronchial epithelial cell azithromycin (AZM) |
| title | Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes |
| title_full | Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes |
| title_fullStr | Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes |
| title_full_unstemmed | Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes |
| title_short | Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes |
| title_sort | effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes |
| topic | asthma exacerbation antiviral immunity atopy rhinovirus bronchial epithelial cell azithromycin (AZM) |
| url | https://www.frontiersin.org/articles/10.3389/falgy.2025.1605109/full |
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