Defining critical roles for NF‐κB p65 and type I interferon in innate immunity to rhinovirus
Abstract The importance of NF‐κB activation and deficient anti‐viral interferon induction in the pathogenesis of rhinovirus‐induced asthma exacerbations is poorly understood. We provide the first in vivo evidence in man and mouse that rhinovirus infection enhanced bronchial epithelial cell NF‐κB p65...
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| Format: | Article |
| Language: | English |
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Springer Nature
2012-11-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1002/emmm.201201650 |
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| author | Nathan W. Bartlett Louise Slater Nicholas Glanville Jennifer J. Haas Gaetano Caramori Paolo Casolari Deborah L. Clarke Simon D. Message Julia Aniscenko Tatiana Kebadze Jie Zhu Patrick Mallia Joseph P. Mizgerd Maria Belvisi Alberto Papi Sergei V. Kotenko Sebastian L. Johnston Michael R. Edwards |
| author_facet | Nathan W. Bartlett Louise Slater Nicholas Glanville Jennifer J. Haas Gaetano Caramori Paolo Casolari Deborah L. Clarke Simon D. Message Julia Aniscenko Tatiana Kebadze Jie Zhu Patrick Mallia Joseph P. Mizgerd Maria Belvisi Alberto Papi Sergei V. Kotenko Sebastian L. Johnston Michael R. Edwards |
| author_sort | Nathan W. Bartlett |
| collection | DOAJ |
| description | Abstract The importance of NF‐κB activation and deficient anti‐viral interferon induction in the pathogenesis of rhinovirus‐induced asthma exacerbations is poorly understood. We provide the first in vivo evidence in man and mouse that rhinovirus infection enhanced bronchial epithelial cell NF‐κB p65 nuclear expression, NF‐κB p65 DNA binding in lung tissue and NF‐κB‐regulated airway inflammation. In vitro inhibition of NF‐κB reduced rhinovirus‐induced pro‐inflammatory cytokines but did not affect type I/III interferon induction. Rhinovirus‐infected p65‐deficient mice exhibited reduced neutrophilic inflammation, yet interferon induction, antiviral responses and virus loads were unaffected, indicating that NF‐κB p65 is required for pro‐inflammatory responses, but redundant in interferon induction by rhinoviruses in vivo. Conversely, IFNAR1−/− mice exhibited enhanced neutrophilic inflammation with impaired antiviral immunity and increased rhinovirus replication, demonstrating that interferon signalling was critical to antiviral immunity. We thus provide new mechanistic insights into rhinovirus infection and demonstrate the therapeutic potential of targeting NF‐κB p65 (to suppress inflammation but preserve anti‐viral immunity) and type I IFN signalling (to enhance deficient anti‐viral immunity) to treat rhinovirus‐induced exacerbations of airway diseases. See accompanying article http://dx.doi.org/10.1002/emmm.201202032 |
| format | Article |
| id | doaj-art-0ec2c26245a34afd8764bd89457e54ee |
| institution | OA Journals |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2012-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-0ec2c26245a34afd8764bd89457e54ee2025-08-20T02:18:35ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842012-11-014121244126010.1002/emmm.201201650Defining critical roles for NF‐κB p65 and type I interferon in innate immunity to rhinovirusNathan W. Bartlett0Louise Slater1Nicholas Glanville2Jennifer J. Haas3Gaetano Caramori4Paolo Casolari5Deborah L. Clarke6Simon D. Message7Julia Aniscenko8Tatiana Kebadze9Jie Zhu10Patrick Mallia11Joseph P. Mizgerd12Maria Belvisi13Alberto Papi14Sergei V. Kotenko15Sebastian L. Johnston16Michael R. Edwards17Department of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonSezione di Malattie dell'Apparato Respiratorio, Centro per lo Studio delle Malattie Infiammatorie Croniche delle Vie Aeree e Patologie Fumo Correlate dell'Apparato Respiratorio (CEMICEF), University of FerraraSezione di Malattie dell'Apparato Respiratorio, Centro per lo Studio delle Malattie Infiammatorie Croniche delle Vie Aeree e Patologie Fumo Correlate dell'Apparato Respiratorio (CEMICEF), University of FerraraCentre for Respiratory Infections, Imperial College LondonDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonThe Pulmonary Centre, Boston University School of MedicineCentre for Respiratory Infections, Imperial College LondonSezione di Malattie dell'Apparato Respiratorio, Centro per lo Studio delle Malattie Infiammatorie Croniche delle Vie Aeree e Patologie Fumo Correlate dell'Apparato Respiratorio (CEMICEF), University of FerraraDepartment of Biochemistry and Molecular Biology, University Hospital Cancer Center, UMDNJ‐New Jersey Medical SchoolDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonDepartment of Respiratory Medicine, National Heart Lung Institute, Imperial College LondonAbstract The importance of NF‐κB activation and deficient anti‐viral interferon induction in the pathogenesis of rhinovirus‐induced asthma exacerbations is poorly understood. We provide the first in vivo evidence in man and mouse that rhinovirus infection enhanced bronchial epithelial cell NF‐κB p65 nuclear expression, NF‐κB p65 DNA binding in lung tissue and NF‐κB‐regulated airway inflammation. In vitro inhibition of NF‐κB reduced rhinovirus‐induced pro‐inflammatory cytokines but did not affect type I/III interferon induction. Rhinovirus‐infected p65‐deficient mice exhibited reduced neutrophilic inflammation, yet interferon induction, antiviral responses and virus loads were unaffected, indicating that NF‐κB p65 is required for pro‐inflammatory responses, but redundant in interferon induction by rhinoviruses in vivo. Conversely, IFNAR1−/− mice exhibited enhanced neutrophilic inflammation with impaired antiviral immunity and increased rhinovirus replication, demonstrating that interferon signalling was critical to antiviral immunity. We thus provide new mechanistic insights into rhinovirus infection and demonstrate the therapeutic potential of targeting NF‐κB p65 (to suppress inflammation but preserve anti‐viral immunity) and type I IFN signalling (to enhance deficient anti‐viral immunity) to treat rhinovirus‐induced exacerbations of airway diseases. See accompanying article http://dx.doi.org/10.1002/emmm.201202032https://doi.org/10.1002/emmm.201201650asthmainflammationinterferonNF‐kappaBrhinovirus |
| spellingShingle | Nathan W. Bartlett Louise Slater Nicholas Glanville Jennifer J. Haas Gaetano Caramori Paolo Casolari Deborah L. Clarke Simon D. Message Julia Aniscenko Tatiana Kebadze Jie Zhu Patrick Mallia Joseph P. Mizgerd Maria Belvisi Alberto Papi Sergei V. Kotenko Sebastian L. Johnston Michael R. Edwards Defining critical roles for NF‐κB p65 and type I interferon in innate immunity to rhinovirus EMBO Molecular Medicine asthma inflammation interferon NF‐kappaB rhinovirus |
| title | Defining critical roles for NF‐κB p65 and type I interferon in innate immunity to rhinovirus |
| title_full | Defining critical roles for NF‐κB p65 and type I interferon in innate immunity to rhinovirus |
| title_fullStr | Defining critical roles for NF‐κB p65 and type I interferon in innate immunity to rhinovirus |
| title_full_unstemmed | Defining critical roles for NF‐κB p65 and type I interferon in innate immunity to rhinovirus |
| title_short | Defining critical roles for NF‐κB p65 and type I interferon in innate immunity to rhinovirus |
| title_sort | defining critical roles for nf κb p65 and type i interferon in innate immunity to rhinovirus |
| topic | asthma inflammation interferon NF‐kappaB rhinovirus |
| url | https://doi.org/10.1002/emmm.201201650 |
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