The S. aureus serine protease-like protein B (SplB) is a potent allergen causing eosinophilic airway inflammation in mice Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.1101/2025.09.10.675349
Asthma is a chronic inflammatory disease associated with increased Staphylococcus aureus airway colonization. However, the causal relationship is unknown. S. aureus secretes several virulence factors that promote allergic sensitization. These include the serine protease-like protein (Spl) B, a secreted protease that elicits a type 2-biased immune response in humans. We studied the allergenic properties of SplB in a mouse model of chronic allergic airway inflammation (AAI). We induced AAI by repeated intratracheal inoculations of recombinant SplB in C57BL/6J mice, wild-type, Rag2 ko, IL-33 ko, and PAR2 ko. We also exposed wild-type mice to an enzymatically inactive mutant of SplB. Airway inflammation was assessed by flow cytometry and airway hyperreactivity measurements. The specific antibody response was characterized by ELISA. We observed severe eosinophil inflammation in the airways and lungs of SplB-sensitized mice, as well as airway hypersensitivity and high SplB-specific serum IgE titers. Remarkably, SplB induced this asthma phenotype without the need for adjuvants. Characterization of the pathomechanisms revealed that the proteolytic activity of SplB and a functional adaptive immune system were essential for the development of murine asthma. The soluble protease sensor IL-33 was necessary for eosinophil tissue invasion, whereas the membrane-bound protease sensor PAR2 was dispensable. Based on these results, we propose a new mechanism to explain the relationship between S. aureus colonization and asthma: S. aureus itself can cause allergic airway inflammation via its potent allergen SplB.
Related Topics
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.09.10.675349
- https://www.biorxiv.org/content/biorxiv/early/2025/09/16/2025.09.10.675349.full.pdf
- OA Status
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- References
- 53
- OpenAlex ID
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Raw OpenAlex JSON
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https://doi.org/10.1101/2025.09.10.675349Digital Object Identifier
- Title
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The S. aureus serine protease-like protein B (SplB) is a potent allergen causing eosinophilic airway inflammation in miceWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-09-16Full publication date if available
- Authors
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J.M. Fournier, Christopher Saade, Hannes Wolfgramm, M. Schilling, Sonja Buchholz, Susanne Neumeister, Yves Laumonnier, Henry J. McSorley, Leif Steil, Matthias Sendler, Uwe Völker, Murthy N. Darisipudi, Barbara M. BrökerList of authors in order
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https://doi.org/10.1101/2025.09.10.675349Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2025/09/16/2025.09.10.675349.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2025/09/16/2025.09.10.675349.full.pdfDirect OA link when available
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0Total citation count in OpenAlex
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53Number of works referenced by this work
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