PMID- 33072128 OWN - NLM STAT- MEDLINE DCOM- 20210622 LR - 20210622 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Mouse Strain-Dependent Difference Toward the Staphylococcus aureus Allergen Serine Protease-Like Protein D Reveals a Novel Regulator of IL-33. PG - 582044 LID - 10.3389/fimmu.2020.582044 [doi] LID - 582044 AB - 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. CI - Copyright (c) 2020 Teufelberger, Van Nevel, Hulpiau, Nordengrun, Savvides, De Graeve, Akula, Holtappels, De Ruyck, Declercq, Vandenabeele, Hellman, Broker, Krysko, Bachert and Krysko. FAU - Teufelberger, Andrea R AU - Teufelberger AR AD - Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium. FAU - Van Nevel, Sharon AU - Van Nevel S AD - Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium. FAU - Hulpiau, Paco AU - Hulpiau P AD - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. AD - Howest, University College West Flanders, Bruges, Belgium. FAU - Nordengrun, Maria AU - Nordengrun M AD - Department of Immunology, University Medicine Greifswald, Greifswald, Germany. FAU - Savvides, Savvas N AU - Savvides SN AD - Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, Belgium. AD - Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium. FAU - De Graeve, Sarah AU - De Graeve S AD - Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium. FAU - Akula, Srinivas AU - Akula S AD - The Biomedical Center, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden. FAU - Holtappels, Gabriele AU - Holtappels G AD - Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium. FAU - De Ruyck, Natalie AU - De Ruyck N AD - Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium. FAU - Declercq, Wim AU - Declercq W AD - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. AD - Molecular Signaling and Cell Death Unit, VIB Center for Inflammation Research, Ghent, Belgium. FAU - Vandenabeele, Peter AU - Vandenabeele P AD - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. AD - Molecular Signaling and Cell Death Unit, VIB Center for Inflammation Research, Ghent, Belgium. FAU - Hellman, Lars AU - Hellman L AD - The Biomedical Center, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden. FAU - Broker, Barbara M AU - Broker BM AD - Department of Immunology, University Medicine Greifswald, Greifswald, Germany. FAU - Krysko, Dmitri V AU - Krysko DV AD - Cell Death Investigation and Therapy Laboratory, Department of Regeneration and Repair, Ghent University, Ghent, Belgium. AD - Cancer Research Institute Ghent, Ghent, Belgium. AD - Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhni Novgorod, Nizhny Novgorod, Russia. FAU - Bachert, Claus AU - Bachert C AD - Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium. AD - International Airway Research Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. AD - Department of Ear, Nose and Throat Diseases, Karolinska University Hospital, Stockholm, Sweden. FAU - Krysko, Olga AU - Krysko O AD - Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium. AD - Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhni Novgorod, Nizhny Novgorod, Russia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200925 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Allergens) RN - 0 (Bacterial Proteins) RN - 0 (Il33 protein, mouse) RN - 0 (Interleukin-33) RN - 0 (Serpins) RN - EC 3.4.- (Peptide Hydrolases) RN - EC 3.4.- (Serine Proteases) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.- (mast cell protease 4) SB - IM MH - Allergens/*immunology MH - Animals MH - Asthma/immunology MH - Bacterial Proteins/*immunology MH - Female MH - Frameshift Mutation/immunology MH - Interleukin-33/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Inbred CBA MH - Mice, Inbred DBA MH - Peptide Hydrolases/immunology MH - Serine Endopeptidases/immunology MH - Serine Proteases/*immunology MH - Serpins/immunology MH - Staphylococcal Infections/*immunology MH - Staphylococcus aureus/*immunology PMC - PMC7544847 OTO - NOTNLM OT - IL-33 OT - S. aureus OT - SplD OT - allergy OT - asthma OT - type 2 immunity EDAT- 2020/10/20 06:00 MHDA- 2021/06/23 06:00 PMCR- 2020/01/01 CRDT- 2020/10/19 05:56 PHST- 2020/07/10 00:00 [received] PHST- 2020/08/24 00:00 [accepted] PHST- 2020/10/19 05:56 [entrez] PHST- 2020/10/20 06:00 [pubmed] PHST- 2021/06/23 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.582044 [doi] PST - epublish SO - Front Immunol. 2020 Sep 25;11:582044. doi: 10.3389/fimmu.2020.582044. eCollection 2020.