Journal of allergy and clinical immunology, 2013-02, Vol.131 (2), p.549-561
2013
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- Autor(en) / Beteiligte
- Titel
- Distinct TLR-mediated pathways regulate house dust mite–induced allergic disease in the upper and lower airways
- Ist Teil von
- Journal of allergy and clinical immunology, 2013-02, Vol.131 (2), p.549-561
- Ort / Verlag
- New York, NY: Mosby, Inc
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Background Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways . In contrast to this general concept, we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different. Objective We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)–induced AR and allergic asthma (AA), respectively. Methods We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts. Results HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2–generated reactive oxygen species mediate both β-glucan–induced TLR2 activation and LPS-induced TLR4 activation. Conclusions We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2–mediated reactive oxygen species.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0091-6749eISSN: 1097-6825DOI: 10.1016/j.jaci.2012.07.050Titel-ID: cdi_proquest_miscellaneous_1284287874
- Format
- –
- Schlagworte
- allergic asthma, Allergic rhinitis, Allergies, Allergy and Immunology, Animals, Asthma, Asthma - immunology, Asthma - metabolism, beta-Glucans - immunology, beta-Glucans - metabolism, Biological and medical sciences, dual oxidase 2, Dual Oxidases, Epithelial Cells - immunology, Epithelial Cells - metabolism, epithelium, Fundamental and applied biological sciences. Psychology, Fundamental immunology, Gene expression, house dust mite, Hypersensitivity - immunology, Hypersensitivity - metabolism, Immune system, Immunity, Innate - immunology, Immunopathology, innate immunity, Lipids, Lipopolysaccharides - immunology, Lung - immunology, Lung - metabolism, Medical sciences, Mice, NADPH Oxidases - immunology, NADPH Oxidases - metabolism, Nasal Mucosa - immunology, Nasal Mucosa - metabolism, Non tumoral diseases, Otorhinolaryngology. Stomatology, pathogen associated molecular pattern, Pyroglyphidae - immunology, reactive oxygen species, Reactive Oxygen Species - immunology, Reactive Oxygen Species - metabolism, Respiratory Mucosa - immunology, Respiratory Mucosa - metabolism, Respiratory System - immunology, Respiratory System - metabolism, Rhinitis, Allergic, Rhinitis, Allergic, Perennial - immunology, Rhinitis, Allergic, Perennial - metabolism, Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis, Toll-like receptor, Toll-Like Receptor 2 - immunology, Toll-Like Receptor 2 - metabolism, Toll-Like Receptor 4 - immunology, Toll-Like Receptor 4 - metabolism, Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology, β-glucans