Extracellular vesicles derived from Staphylococcus aureus induce atopic dermatitis-like skin inflammation

Abstract

BackgroundRecently, we found that Staphylococcus aureus produces extracellular vesicles (EV) that contain pathogenic proteins. Although S. aureus infection has been linked with atopic dermatitis (AD), the identities of the causative agents from S. aureus are controversial. We evaluated whether S. aureus-derived EV are causally related to the pathogenesis of AD.MethodsExtracellular vesicles were isolated by the ultracentrifugation of S. aureus culture media. The EV were applied three times per week to tape-stripped mouse skin. Inflammation and immune dysfunction were evaluated 48 h after the final application in hairless mice. Extracellular vesicles-specific IgE levels were measured by ELISA in AD patients and healthy subjects.ResultsThe in vitro application of S. aureus EV increased the production of pro-inflammatory mediators (IL-6, thymic stromal lymphopoietin, macrophage inflammatory protein-1α, and eotaxin) by dermal fibroblasts. The in vivo application of S. aureus EV after tape stripping caused epidermal thickening with infiltration of the dermis by mast cells and eosinophils in mice. These changes were associated with the enhanced cutaneous production of IL-4, IL-5, IFN-γ, and IL-17. Interestingly, the serum levels of S. aureus EV-specific IgE were significantly increased in AD patients relative to healthy subjects.ConclusionThese results indicate that S. aureus EV induce AD-like inflammation in the skin and that S. aureus-derived EV are a novel diagnostic and therapeutic target for the control of AD.

Immunization with Escherichia coli Outer Membrane Vesicles Protects Bacteria-Induced Lethality via Th1 and Th17 Cell Responses

“…Proteomic analysis revealed that extracellular vesicles derived from S. aureus harbor several pathogenic components (10). Furthermore, S. aureus extracellular vesicles induce atopic dermatitislike skin inflammation in mice (47). These observations provide hints on the possible roles of Gram-positive secreted vesicles as vaccine candidates (10).…”

Extracellular Vesicles Derived from Gram-Negative Bacteria, such asEscherichia coli, Induce Emphysema Mainly via IL-17A–Mediated Neutrophilic Inflammation

“…In addition, our previous work indicates that EVs in indoor dust are important in the development of neutrophilic inflammation in the lung (11). Previously, we also found that the Grampositive bacterium S. aureus produces EVs (9), which may be causally related to atopic dermatitis in the skin (28) and also neutrophilic inflammation in the lung (12). The present study showed that the repeated inhalation of E. coli EVs induced neutrophilic inflammation and thereby emphysema mainly via an IL-17A-dependent mechanism.…”

The role of infection in the pathogenesis of allergodermatoses

“…При этом продукция ТСЛП от-менялась при подавлении активации TLR2 и TLR6 специфическими ингибиторами, что показывает прямую связь повышения уровня ТСЛП с распозна-ванием липопротеинов бактерии. S. aureus также по-вышает уровень экспрессии ТСЛП в фибробластах кожи [36]. Выброс ТСЛП наблюдается также и в от-вет на дрожжеподобные грибы Malassezia, являю-щиеся вторым по значимости микроорганизмом, колонизирующим кожу больных с аллергодермато-зами.…”