Mouse Strain-Dependent Difference Toward the Staphylococcus aureus Allergen Serine Protease-Like Protein D Reveals a Novel Regulator of IL-33

Frontiers in Immunology

Olga Krysko²  Dmitri V. Krysko²  Claus Bachert⁴  Savvas N. Savvides⁶  Maria Nordengrün⁸  Barbara M. Bröker⁸  Paco Hulpiau⁹  Peter Vandenabeele^1,10  Wim Declercq^1,10  Lars Hellman^1,11  Srinivas Akula^1,11  Andrea R. Teufelberger^1,13  Natalie De Ruyck^1,13  Sharon Van Nevel^1,13  Sarah De Graeve^1,13  Gabriele Holtappels^1,13 

[1] 0Cancer Research Institute Ghent, Ghent, Belgium;1Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhni Novgorod, Nizhny Novgorod, Russia;2International Airway Research Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;3Department of Ear, Nose and Throat Diseases, Karolinska University Hospital, Stockholm, Sweden;Cell Death Investigation and Therapy Laboratory, Department of Regeneration and Repair, Ghent University, Ghent, Belgium;Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium;Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium;Department of Immunology, University Medicine Greifswald, Greifswald, Germany;Howest, University College West Flanders, Bruges, Belgium;Molecular Signaling and Cell Death Unit, VIB Center for Inflammation Research, Ghent, Belgium;The Biomedical Center, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden;Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, Belgium;Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium;

关键词: allergy;    asthma;    IL-33;    S. aureus;    SplD;    type 2 immunity;   

DOI  :  10.3389/fimmu.2020.582044

来源: DOAJ

【 摘 要 】

Staphylococcus aureus (S. aureus) can secrete a broad range of virulence factors, among which staphylococcal serine protease-like proteins (Spls) have been identified as bacterial allergens. The S. aureus allergen serine protease-like protein D (SplD) induces allergic asthma in C57BL/6J mice through the IL-33/ST2 signaling axis. Analysis of C57BL/6J, C57BL/6N, CBA, DBA/2, and BALB/c mice treated with intratracheal applications of SplD allowed us to identify a frameshift mutation in the serine (or cysteine) peptidase inhibitor, clade A, and member 3I (Serpina3i) causing a truncated form of SERPINA3I in BALB/c, CBA, and DBA/2 mice. IL-33 is a key mediator of SplD-induced immunity and can be processed by proteases leading to its activation or degradation. Full-length SERPINA3I inhibits IL-33 degradation in vivo in the lungs of SplD-treated BALB/c mice and in vitro by direct inhibition of mMCP-4. Collectively, our results establish SERPINA3I as a regulator of IL-33 in the lungs following exposure to the bacterial allergen SplD, and that the asthma phenotypes of mouse strains may be strongly influenced by the observed frameshift mutation in Serpina3i. The analysis of this protease-serpin interaction network might help to identify predictive biomarkers for type-2 biased airway disease in individuals colonized by S. aureus.

【 授权许可】

Unknown