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Staphylococcus aureus ‐derived membrane vesicles exacerbate skin inflammation in atopic dermatitis
Author(s) -
Jun S. H.,
Lee J. H.,
Kim S. I.,
Choi C. W.,
Park T. I.,
Jung H. R.,
Cho J. W.,
Kim S. H.,
Lee J. C.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12851
Subject(s) - staphylococcus aureus , atopic dermatitis , immunology , cytokine , chemokine , inflammation , epidermis (zoology) , biology , medicine , microbiology and biotechnology , genetics , anatomy , bacteria
Summary Background Skin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis ( AD ). However, the exact mechanisms by which S. aureus can worsen AD are unknown. Objective We investigated whether and how S. aureus ‐derived membrane vesicles ( MV s) contribute to worsening of AD . Methods Immunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A ( SPA ) in the epidermis of AD lesions. HaCaT cells were treated with S. aureus MV s and were analysed for the expression of cytokine genes. Immunopathology and cytokine gene profiles were analysed after topical application of S. aureus MV s to AD ‐like skin lesions in a mouse model. Results The MV component SPA was detected in the keratinocytes as well as in the intercellular space of the epidermis of AD lesions colonized with S. aureus . Intact MV s from S. aureus delivered their components to keratinocytes and stimulated pro‐inflammatory cytokine gene expression in vitro . A knock‐down of Toll‐like receptor 2 or nucleotide‐binding oligomerization domain 2 using small interfering RNA s suppressed interleukin‐8 gene expression. Topical application of intact S. aureus MV s to AD ‐like skin lesions in the mouse model induced massive infiltration of inflammatory cells and the resulting eczematous dermatitis. This inflammatory reaction was associated with a mixed Th1/Th2 immune response and enhanced expression of chemokine genes in AD ‐like skin lesions. Conclusions and Clinical Relevance This study showed the importance of S. aureus MV s as a potent mediator for worsening of AD among many exogenous worsening factors of AD . Thus, S. aureus MV s may be regarded as one of the therapeutic targets for the management of AD aggravation.