Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Σάββατο 20 Μαΐου 2017

The IL-33/ST2 axis is crucial in type 2 airway responses induced by the Staphylococcus aureus protease SplD

Publication date: Available online 19 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Andrea R. Teufelberger, Maria Nordengrün, Harald Braun, Tania Maes, Katrien De Grove, Gabriele Holtappels, Clara O'Brien, Sharen Provoost, Hamida Hammad, Amanda Gonçalves, Rudi Beyaert, Wim Declercq, Peter Vandenabeele, Dmitri V. Krysko, Barbara M. Bröker, Claus Bachert, Olga Krysko
BackgroundChronic airway inflammatory diseases such as chronic rhinosinusitis with nasal polyps and asthma showed increased nasal Staphylococcus aureus (S. aureus) colonization. Serine protease like protein D (SplD) and other closely related proteases secreted by S. aureus have recently been identified as inducers of allergic asthma in humans and mice but their mechanism of action is largely unknown.ObjectiveWe investigated the role of recombinant SplD in driving Th2-biased responses and IgE formation in a murine model of allergic asthma.MethodsAllergic asthma was induced in C57BL/6 J wild type mice, TLR4 knockout mice (TLR4-/-) and Rag2 knockout mice (Rag2-/-) by repeated intratracheal applications of SplD. Inflammatory parameters in the airways were assessed by flow cytometry, ELISA, Luminex and immunohistochemistry. Serum SplD-specific IgE levels were analysed by ELISA.ResultsWe observed that repeated intratracheal exposure to SplD led to IL-33 and eotaxin production, eosinophilia, bronchial hyperreactivity and goblet cell hyperplasia in the airways. Blocking the IL-33 activity using a soluble ST2 receptor (sST2) significantly decreased the numbers of eosinophils, IL-13+ILC2s, IL-13+CD4+ T cells, and IL-5 and IL-13 production by lymph node cells but had no effect on IgE production. SplD-induced airway inflammation and IgE production were largely dependent on the presence of the functional adaptive immune system and independent of TLR4 signalling.ConclusionThe S. aureus-derived protein SplD is a potent allergen of S. aureus and induces a Th2-biased inflammatory response in the airways in an IL-33-dependent, but TRL4-independent manner. sST2 could be an efficient strategy to interfere with SplD-induced Th2 inflammation, but does not prevent the allergic sensitization.

Graphical abstract

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Teaser

S.aureus protein SplD acts as an allergen and an adjuvant inducing asthma features via inducing IL-33 production by airway epithelial cells. Soluble IL-33 receptor is a promising treatment option as it interferes with SplD-induced inflammation.


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