The IL-33/ST2 axis is crucial in type 2 airway responses induced by Staphylococcus aureus-derived serine protease-like protein D.

Abstract

BACKGROUND:

Chronic airway inflammatory diseases, such as chronic rhinosinusitis with nasal polyps and asthma, show increased nasal Staphylococcus aureus colonization. Staphylococcus aureus-derived serine protease-like protein (Spl) D and other closely related proteases secreted by S aureus have recently been identified as inducers of allergic asthma in human subjects 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, Toll-like receptor (TLR) 4 knockout (Tlr4-/-) mice, and recombination-activating gene (Rag2) knockout (Rag2-/-) mice by means of repeated intratracheal applications of SplD. Inflammatory parameters in the airways were assessed by means of flow cytometry, ELISA, Luminex, and immunohistochemistry. Serum SplD-specific IgE levels were analyzed by using 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 IL-33 activity with a soluble ST2 receptor significantly decreased the numbers of eosinophils, IL-13+ type 2 innate lymphoid cells and 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 signaling.

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. The soluble ST2 receptor could be an efficient strategy to interfere with SplD-induced TH2 inflammation but does not prevent the allergic sensitization.

• Authors: 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
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 141 Issue 2 Pg. 549-559.e7 (02 2018) ISSN: 1097-6825 [Electronic] United States
• PMID: 28532656 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Bacterial Proteins
• Il1rl1 protein, mouse
• Il33 protein, mouse
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-33
• Serine Proteases

Topics

• Animals
• Asthma (chemically induced, genetics, immunology)
• Bacterial Proteins (toxicity)
• CD4-Positive T-Lymphocytes (immunology, pathology)
• Disease Models, Animal
• Interleukin-1 Receptor-Like 1 Protein (genetics, immunology)
• Interleukin-33 (genetics, immunology)
• Mice
• Mice, Knockout
• Serine Proteases (toxicity)
• Signal Transduction (drug effects, genetics)
• Staphylococcus aureus (immunology, pathogenicity)
• Th2 Cells (immunology, pathology)