期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 128, 期 1, 页码 82-U141出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2011.02.034
关键词
Staphylococcus aureus; atopic dermatitis; bacterial antigen; bacterial allergen; allergy; IgE; superinfection; superantigen
资金
- Austrian Science Fund [F1804, F1815, F1818, P20011-B13]
- Christian Doppler Research Association, Vienna, Austria
- Biomay, Vienna, Austria
- Biomay AG
- Christian Doppler Forschungsgesellschaft
- Austrian Science Foundation
- German Research Council
- Bundesministerium fur Bildung und Forschung
- Christian Doppler Research Association
- Biomay
- Phadia
- Austrian Science Fund (FWF) [P20011] Funding Source: Austrian Science Fund (FWF)
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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