Spls are pacemakers of allergic airway reactions to Staphylococcus aureus

Publication date: Available online 10 May 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Sebastian Stentzel, Andrea Teufelberger, Maria Nordengrün, Julia Kolata, Frank Schmidt, Koen van Crombruggen, Stephan Michalik, Jana Kumpfmüller, Sebastian Tischer, Thomas Schweder, Michael Hecker, Susanne Engelmann, Uwe Völker, Olga Krysko, Claus Bachert, Barbara M. Bröker
BackgroundA substantial subgroup of asthma patients suffers from "non-allergic" or idiopathic asthma, which often takes a severe course and is difficult to treat. The cause may 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.ObjectiveTo search for potentially allergenic S. aureus proteins and characterize the immune response directed against them.MethodsTo screen for potential bacterial allergens, S. aureus extracellular proteins targeted by human serum IgG4 were identified by immunoblotting. Candidate antigens were expressed as recombinant proteins and used to analyze the established cellular and humoral immune responses in healthy adults and asthma patients. The ability to induce a type 2 immune response in vivo was tested in a mouse asthma model.ResultsWe identified staphylococcal serine protease-like proteins (Spls) as dominant IgG4-binding S. aureus proteins. The Spls A-F are extracellular proteases of unknown function that are expressed by S. aureus in vivo. Spls elicited IgE antibody responses in most asthma patients. In healthy S. aureus carriers and non-carriers, peripheral blood T cells elaborated Th2 cytokines following 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.ConclusionWe identify Spls as triggering allergens released by S. aureus, opening prospects for diagnosis and causal therapy of asthma.

Teaser

Serine protease-like proteins (Spls) of Staphylococcus aureus are identified as allergens eliciting type 2 inflammation in healthy and asthmatic individuals as well as in mice. This knowledge may advance diagnosis and treatment of difficult-to-treat asthma.


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