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

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

J Allergy Clin Immunol. 2017 May 19;:

Authors: Teufelberger AR, Nordengrün M, Braun H, Maes T, De Grove K, Holtappels G, O'Brien C, Provoost S, Hammad H, Gonçalves A, Beyaert R, Declercq W, Vandenabeele P, Krysko DV, Bröker BM, Bachert C, Krysko O

Abstract
BACKGROUND: Chronic 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.
OBJECTIVE: We investigated the role of recombinant SplD in driving Th2-biased responses and IgE formation in a murine model of allergic asthma.
METHODS: Allergic 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.
RESULTS: We 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.
CONCLUSION: The 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.

PMID: 28532656 [PubMed - as supplied by publisher]

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