Staphylococcal serine protease-like proteins are pacemakers of allergic airway reactions to Staphylococcus aureus.
A substantial subgroup of asthmatic patients have "nonallergic" or idiopathic asthma, which often takes a severe course and is difficult to treat. The cause might be allergic reactions to the gram-positive pathogen Staphylococcus aureus, a frequent colonizer of the upper airways. However, the driving allergens of S aureus have remained elusive.



We sought to search for potentially allergenic S aureus proteins and characterize the immune response directed against them.



S aureus extracellular proteins targeted by human serum IgG4were identified by means of immunoblotting to screen for potential bacterial allergens. Candidate antigens were expressed as recombinant proteins and used to analyze the established cellular and humoral immune responses in healthy adults and asthmatic patients. The ability to induce a type 2 immune response in vivo was tested in a mouse asthma model.



We identified staphylococcal serine protease-like proteins (Spls) as dominant IgG4-binding S aureus proteins. SplA through SplF are extracellular proteases of unknown function expressed by S aureus in vivo. Spls elicited IgE antibody responses in most asthmatic patients. In healthy S aureus carriers and noncarriers, peripheral blood T cells elaborated TH2 cytokines after stimulation with Spls, as is typical for allergens. In contrast, TH1/TH17 cytokines, which dominated the response to S aureus α-hemolysin, were of low concentration or absent. In mice inhalation of SplD without adjuvant induced lung inflammation characterized by TH2 cytokines and eosinophil infiltration.



We identify Spls as triggering allergens released by S aureus, opening prospects for diagnosis and causal therapy of asthma.
Department of Immunology, University Medicine Greifswald, Greifswald, Germany.
Sebastian
S
Stentzel
Upper Airways Research Laboratory, Ghent University, Ghent, Belgium.
Andrea
A
Teufelberger
Department of Immunology, University Medicine Greifswald, Greifswald, Germany.
Maria
M
Nordengrün
Department of Immunology, University Medicine Greifswald, Greifswald, Germany; Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Julia
J
Kolata
Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany; Junior Group Applied Proteomics, ZIK FunGene, University Medicine Greifswald, Greifswald, Germany.
Frank
F
Schmidt
Upper Airways Research Laboratory, Ghent University, Ghent, Belgium.
Koen
K
van Crombruggen
Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany; Junior Group Applied Proteomics, ZIK FunGene, University Medicine Greifswald, Greifswald, Germany.
Stephan
S
Michalik
Department of Pharmaceutical Biotechnology, Institute of Pharmacy, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany; Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Jena, Germany.
Jana
J
Kumpfmüller
Department of Immunology, University Medicine Greifswald, Greifswald, Germany.
Sebastian
S
Tischer
Department of Pharmaceutical Biotechnology, Institute of Pharmacy, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
Thomas
T
Schweder
Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
Michael
M
Hecker
Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany; Institute for Microbiology, University of Braunschweig, Braunschweig, Germany; Helmholtz Center for Infection Research, Microbial Proteomics, Braunschweig, Germany.
Susanne
S
Engelmann
Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Uwe
U
Völker
Upper Airways Research Laboratory, Ghent University, Ghent, Belgium.
Olga
O
Krysko
Upper Airways Research Laboratory, Ghent University, Ghent, Belgium; Division of Ear, Nose, and Throat Diseases, Clintec, Karolinska Institute, Stockholm, Sweden.
Claus
C
Bachert
Department of Immunology, University Medicine Greifswald, Greifswald, Germany. Electronic address: broeker@uni-greifswald.de.
Barbara M
BM
Bröker
D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011485:Protein Binding; D057057:Serine Proteases / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D055815:Young Adult
D000485:Allergens; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D057057:Serine Proteases
Asthma; IgE; Staphylococcus aureus; serine protease-like proteins; type 2 inflammation