Staphylococcus aureus fibronectin-binding protein specifically binds IgE from patients with atopic dermatitis and requires antigen presentation for cellular immune responses

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:128

Article

Reginald, Kavita¹  Westritschnig, Kerstin¹  Linhart, Birgit¹  Focke-Tejkl, Margarete²  Jahn-Schmid, Beatrice¹  Eckl-Dorna, Julia³  Heratizadeh, Annice¹⁰  Stoecklinger, Angelika⁶  Balic, Nadja⁴  Spitzauer, Susanne⁴  Niederberger, Verena³  Werfel, Thomas¹⁰  Thalhamer, Josef⁶  Weidinger, Stephan⁸  Novak, Natalija⁹  Ollert, Markus^7,8  Hirschl, Alexander M.⁵  Valenta, Rudolf^1,2 

[1] Med Univ Vienna, Div Immunopathol, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, A-1090 Vienna, Austria

[2] Med Univ Vienna, Christian Doppler Lab Allergy Res, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, A-1090 Vienna, Austria

[3] Med Univ Vienna, Dept Otorhinolaryngol, A-1090 Vienna, Austria

[4] Med Univ Vienna, Inst Med & Chem Lab Diagnost, A-1090 Vienna, Austria

[5] Med Univ Vienna, Dept Clin Microbiol, A-1090 Vienna, Austria

[6] Salzburg Univ, Dept Mol Biol, A-5020 Salzburg, Austria

[7] Tech Univ Munich, Clin Res Div Mol & Clin Allergotoxicol, Munich, Germany

[8] Tech Univ Munich, Dept Dermatol & Allergy, Munich, Germany

[9] Univ Bonn, Dept Dermatol & Allergy, D-5300 Bonn, Germany

[10] Hannover Med Sch, Div Immunodermatol & Allergy Res, Dept Dermatol & Allergy, Hannover, Germany

关键词: Staphylococcus aureus;    atopic dermatitis;    bacterial antigen;    bacterial allergen;    allergy;    IgE;    superinfection;    superantigen;   

DOI  :  10.1016/j.jaci.2011.02.034

来源: Elsevier

【 摘 要 】

Background: Staphylococcus aureus superinfections occur in more than 90% of patients with atopic dermatitis (AD) and aggravate skin inflammation. S aureus toxins lead to tissue damage and augment T-cell-mediated skin inflammation by a superantigen effect. Objective: To characterize IgE-reactive proteins from S aureus. Methods: A genomic S aureus library was screened with IgE from patients with AD for DNA clones coding for IgE-reactive antigens. One was identified as fibronectin-binding protein (FBP). Recombinant FBP was expressed in Escherichia coli, purified, and tested for specific IgE reactivity in patients with AD. Its allergenic activity was studied in basophil activation experiments and T-cell cultures. The in vivo allergenic activity was investigated by sensitizing mice. Results: Using IgE from patients with AD for screening of a genomic S aureus library, an IgE-reactive DNA clone was isolated that coded for FBP. Recombinant FBP was expressed in E coli and purified. It reacted specifically with IgE from patients with AD and exhibited allergenic activity in basophil degranulation assays. FBP showed specific T-cell reactivity requiring antigen presentation and induced the secretion of proinflammatory cytokines from PBMCs. Mice sensitized with FBP mounted FBP-specific IgE responses, showed FBP-specific basophil degranulation as well as FBP-specific T-cell proliferation, and mixed T(H)2/T(H)1 cytokine secretion. Conclusion: Evidence is provided that specific humoral and cellular immune responses to S aureus antigens dependent on antigen presentation represent a novel mechanism for S aureus-induced skin inflammation in AD. Furthermore, FBP may be used for the development of novel diagnostic and therapeutic strategies for S aureus infections. (J Allergy Clin Immunol 2011; 128: 82-91.)

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