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

Andrea Renate Teufelberger (UGent) , Maria Nordengrün, Harald Braun (UGent) , Tania Maes (UGent) , Katrien De Grove (UGent) , Gabriële Holtappels (UGent) , Clara O'Brien (UGent) , Sharen Provoost (UGent) , Hamida Hammad (UGent) , Amanda Gonçalves (UGent) , et al.
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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 T-H(2)-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 T-H(2)-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 T-H(2) inflammation but does not prevent the allergic sensitization.
Keywords
Allergy, asthma, Staphylococcus aureus, sensitization, serine protease, HOUSE-DUST MITE, THYMIC STROMAL LYMPHOPOIETIN, ALLERGIC LUNG INFLAMMATION, INNATE LYMPHOID-CELLS, ATOPIC-DERMATITIS, IMMUNE-RESPONSES, DENDRITIC CELLS, ENTEROTOXIN-B, IN-VITRO, ASTHMA

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Citation

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Chicago
Teufelberger, Andrea Renate, Maria Nordengrün, Harald Braun, Tania Maes, Katrien De Grove, Gabriële Holtappels, Clara O’Brien, et al. 2018. “The IL-33/ST2 Axis Is Crucial in Type 2 Airway Responses Induced by Staphylococcus Aureus-derived Serine Protease-like Protein D.” Journal of Allergy and Clinical Immunology 141 (2): 549–559.
APA
Teufelberger, A. R., Nordengrün, M., Braun, H., Maes, T., De Grove, K., Holtappels, G., O’Brien, C., et al. (2018). The IL-33/ST2 axis is crucial in type 2 airway responses induced by Staphylococcus aureus-derived serine protease-like protein D. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 141(2), 549–559.
Vancouver
1.
Teufelberger AR, Nordengrün M, Braun H, Maes T, De Grove K, Holtappels G, et al. The IL-33/ST2 axis is crucial in type 2 airway responses induced by Staphylococcus aureus-derived serine protease-like protein D. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2018;141(2):549–59.
MLA
Teufelberger, Andrea Renate, Maria Nordengrün, Harald Braun, et al. “The IL-33/ST2 Axis Is Crucial in Type 2 Airway Responses Induced by Staphylococcus Aureus-derived Serine Protease-like Protein D.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 141.2 (2018): 549–559. Print.
@article{8532401,
  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 T-H(2)-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 T-H(2)-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 T-H(2) inflammation but does not prevent the allergic sensitization.},
  author       = {Teufelberger, Andrea Renate and Nordengr{\"u}n, Maria and Braun, Harald and Maes, Tania and De Grove, Katrien and Holtappels, Gabri{\"e}le and O'Brien, Clara and Provoost, Sharen and Hammad, Hamida and Gon\c{c}alves, Amanda and Beyaert, Rudi and Declercq, Wim and Vandenabeele, Peter and Krysko, Dmitri and Br{\"o}ker, Barbara M and Bachert, Claus and Krysko, Olga},
  issn         = {0091-6749},
  journal      = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
  keyword      = {Allergy,asthma,Staphylococcus aureus,sensitization,serine protease,HOUSE-DUST MITE,THYMIC STROMAL LYMPHOPOIETIN,ALLERGIC LUNG INFLAMMATION,INNATE LYMPHOID-CELLS,ATOPIC-DERMATITIS,IMMUNE-RESPONSES,DENDRITIC CELLS,ENTEROTOXIN-B,IN-VITRO,ASTHMA},
  language     = {eng},
  number       = {2},
  pages        = {549--559},
  title        = {The IL-33/ST2 axis is crucial in type 2 airway responses induced by Staphylococcus aureus-derived serine protease-like protein D},
  url          = {http://dx.doi.org/10.1016/j.jaci.2017.05.004},
  volume       = {141},
  year         = {2018},
}

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