IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation
Alterations of the airway microbiome are often associated with pulmonary diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis in the upper airways is linked with an increased risk to develop or exacerbate asthma. However, the mechanisms by which M. catarrhalis augments al...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01562/full |
| _version_ | 1811322625960443904 |
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| author | Safa Alnahas Stefanie Hagner Hartmann Raifer Ayse Kilic Georg Gasteiger Reinier Mutters Anne Hellhund Immo Prinz Olaf Pinkenburg Alexander Visekruna Holger Garn Ulrich Steinhoff |
| author_facet | Safa Alnahas Stefanie Hagner Hartmann Raifer Ayse Kilic Georg Gasteiger Reinier Mutters Anne Hellhund Immo Prinz Olaf Pinkenburg Alexander Visekruna Holger Garn Ulrich Steinhoff |
| author_sort | Safa Alnahas |
| collection | DOAJ |
| description | Alterations of the airway microbiome are often associated with pulmonary diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis in the upper airways is linked with an increased risk to develop or exacerbate asthma. However, the mechanisms by which M. catarrhalis augments allergic airway inflammation (AAI) remain unclear. We here characterized the cellular and soluble mediators of M. catarrhalis triggered excacerbation of AAI in wt and IL-17 deficient as well as in animals treated with TNF-α and IL-6 neutralizing antibodies. We compared the type of inflammatory response in M. catarrhalis infected, house dust mite (HDM)-allergic and animals infected with M. catarrhalis at different time points of HDM sensitization. We found that airway infection of mice with M. catarrhalis triggers a strong inflammatory response with massive neutrophilic infiltrates, high amounts of IL-6 and TNF-α and moderate levels of CD4+ T-cell-derived IFN-γ and IL-17. If bacterial infection occurred during HDM allergen sensitization, the allergic airway response was exacerbated, particularly by the expansion of Th17 cells and increased TNF-α levels. Neutralization of IL-17 or TNF-α but not IL-6 resulted in accelerated clearance of M. catarrhalis and effectively prevented infection-induced exacerbation of AAI. Taken together, our data demonstrate an essential role for TNF-α and IL-17 in infection-triggered exacerbation of AAI. |
| first_indexed | 2024-04-13T13:39:34Z |
| format | Article |
| id | doaj.art-c3e062a5e4744385bcde50d69b6aa5b6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T13:39:34Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c3e062a5e4744385bcde50d69b6aa5b62022-12-22T02:44:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-11-01810.3389/fimmu.2017.01562271511IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway InflammationSafa Alnahas0Stefanie Hagner1Hartmann Raifer2Ayse Kilic3Georg Gasteiger4Reinier Mutters5Anne Hellhund6Immo Prinz7Olaf Pinkenburg8Alexander Visekruna9Holger Garn10Ulrich Steinhoff11Institute of Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, GermanyInstitute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Member of the German Center for Lung Research, University of Marburg, Marburg, GermanyInstitute of Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, GermanyInstitute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Member of the German Center for Lung Research, University of Marburg, Marburg, GermanyInstitute of Medical Microbiology and Hygiene, FZI Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, GermanyInstitute of Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, GermanyInstitute of Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyInstitute of Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, GermanyInstitute of Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, GermanyInstitute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Member of the German Center for Lung Research, University of Marburg, Marburg, GermanyInstitute of Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, GermanyAlterations of the airway microbiome are often associated with pulmonary diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis in the upper airways is linked with an increased risk to develop or exacerbate asthma. However, the mechanisms by which M. catarrhalis augments allergic airway inflammation (AAI) remain unclear. We here characterized the cellular and soluble mediators of M. catarrhalis triggered excacerbation of AAI in wt and IL-17 deficient as well as in animals treated with TNF-α and IL-6 neutralizing antibodies. We compared the type of inflammatory response in M. catarrhalis infected, house dust mite (HDM)-allergic and animals infected with M. catarrhalis at different time points of HDM sensitization. We found that airway infection of mice with M. catarrhalis triggers a strong inflammatory response with massive neutrophilic infiltrates, high amounts of IL-6 and TNF-α and moderate levels of CD4+ T-cell-derived IFN-γ and IL-17. If bacterial infection occurred during HDM allergen sensitization, the allergic airway response was exacerbated, particularly by the expansion of Th17 cells and increased TNF-α levels. Neutralization of IL-17 or TNF-α but not IL-6 resulted in accelerated clearance of M. catarrhalis and effectively prevented infection-induced exacerbation of AAI. Taken together, our data demonstrate an essential role for TNF-α and IL-17 in infection-triggered exacerbation of AAI.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01562/fullexacerbation of pulmonary inflammationIL-17TNF-αMoraxellaceae infectionsinfection and allergyexacerbation of allergic reactions |
| spellingShingle | Safa Alnahas Stefanie Hagner Hartmann Raifer Ayse Kilic Georg Gasteiger Reinier Mutters Anne Hellhund Immo Prinz Olaf Pinkenburg Alexander Visekruna Holger Garn Ulrich Steinhoff IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation Frontiers in Immunology exacerbation of pulmonary inflammation IL-17 TNF-α Moraxellaceae infections infection and allergy exacerbation of allergic reactions |
| title | IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation |
| title_full | IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation |
| title_fullStr | IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation |
| title_full_unstemmed | IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation |
| title_short | IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation |
| title_sort | il 17 and tnf α are key mediators of moraxella catarrhalis triggered exacerbation of allergic airway inflammation |
| topic | exacerbation of pulmonary inflammation IL-17 TNF-α Moraxellaceae infections infection and allergy exacerbation of allergic reactions |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01562/full |
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