IL-17 and TNF-alpha are essential mediators of M. catarrhalis triggered exacerbation of HDM allergic airway inflammation

In this study we have demonstrated in a murine model of allergic airway inflammation that intranasal infection with the human pathogen M. catarrhalis exacerbate pulmonary inflammation. The aim of the study was: i) to establish an animal model of infection induced exacerbation of lung allergic re...

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Bibliographic Details
Main Author: Alnahas, Safa
Contributors: Steinhoff, Ulrich (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Language:English
Published: Philipps-Universität Marburg 2017
Hygiene u. Med. Mikrobiologie mit Medizinaluntersuchungsamt
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Summary:In this study we have demonstrated in a murine model of allergic airway inflammation that intranasal infection with the human pathogen M. catarrhalis exacerbate pulmonary inflammation. The aim of the study was: i) to establish an animal model of infection induced exacerbation of lung allergic reactions, ii) to study the pulmonary immune responses of HDM allergic animals with and without infection and iii) to identify potential targets to prevent exacerbation of lung inflammation. The essential findings are that the human pathogen, M. catarrhalis, is able to colonize murine lungs for approximately 6 days and thus can be used as a model germ for acute respiratory infection. We further could show, that infection with M. catarrhalis exacerbates allergic airway inflammation (AAI) via innate and adaptive immune responses, depending on the time of infection, i.e. before, during or after established allergic sensitization. While M. catarrhalis infection in a non-allergic environment induced high amounts of IL-6 and TNF- but moderate amounts of T cell derived IFN- and IL-17, infection triggered exacerbation of AAI mainly by IL-17 and TNF- but not IL-6. Further, we could show that lack of IL-17 or neutralization of TNF- but not IL-6 is able to prevent M. catarrhalis induced exacerbation of AAI. In conclusion, infection with M. catarrhalis has the potential to exacerbate allergic airway inflammation at any time of infection and temporary treatment with anti-IL-17 and/or anti- TNF- antibodies may be appropriate to prevent aggravation of this lung disease.
DOI:https://doi.org/10.17192/z2017.0395