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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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MLA
Teufelberger, Andrea Renate, 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, vol. 141, no. 2, 2018, pp. 549–59.
APA
Teufelberger, A. R., Nordengrün, M., Braun, H., Maes, T., De Grove, K., Holtappels, G., … Krysko, O. (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.
Chicago author-date
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): 549–59.
Chicago author-date (all authors)
Teufelberger, Andrea Renate, Maria Nordengrün, Harald Braun, Tania Maes, Katrien De Grove, Gabriële Holtappels, Clara O’Brien, Sharen Provoost, Hamida Hammad, Amanda Gonçalves, Rudi Beyaert, Wim Declercq, Peter Vandenabeele, Dmitri Krysko, Barbara M Bröker, Claus Bachert, and Olga Krysko. 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.
IEEE
[1]
A. R. Teufelberger 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, vol. 141, no. 2, pp. 549–559, 2018.
@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 Nordengrün, Maria and Braun, Harald and Maes, Tania and De Grove, Katrien and Holtappels, Gabriële and O'Brien, Clara and Provoost, Sharen and Hammad, Hamida and Gonçalves, Amanda and Beyaert, Rudi and Declercq, Wim and Vandenabeele, Peter and Krysko, Dmitri and Bröker, Barbara M and Bachert, Claus and Krysko, Olga},
  issn         = {0091-6749},
  journal      = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
  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},
  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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