Staphylococcus aureus-derived extracellular vesicles induce neutrophilic pulmonary inflammation via both Th1 and Th17 cell responses
Staphylococcus aureus-derived extracellular vesicles induce neutrophilic pulmonary inflammation via both Th1 and Th17 cell responses
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DOI：
10.1111/all.12001
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发表时间：
2012-10-01
期刊：
影响因子：
12.4
通讯作者：
Kim, Y. -K.
中科院分区：
文献类型：
--
作者：
Kim, M. -R.;Hong, S. -W.;Kim, Y. -K.
研究背景金黄色葡萄球菌是人类最重要的病原菌之一，它能分泌囊泡进入细胞外环境。目的评价吸入S.金黄色葡萄球菌来源的细胞外囊泡（EV）与炎性肺病的发病机制有因果关系。方法采用序贯超滤-超离心法制备金黄色葡萄球菌EV。在体外评价EV应用于气道上皮细胞和肺泡巨噬细胞后的天然免疫应答。在呼吸道暴露于EV后，评价体内先天性和适应性免疫应答。在用S.金黄色葡萄球菌EV和卵清蛋白（OVA）。结果金黄色葡萄球菌和S.室内灰尘中检出金黄色EV。在体外用S. aureus EV，而气道上皮细胞仅产生IL-6。反复气道暴露于S。金黄色葡萄球菌EV主要通过Toll样受体2（TLR2）依赖性机制诱导Th1和Th17细胞应答以及嗜肺性炎症。在佐剂效应方面，S.金黄色葡萄球菌EV和OVA在单独的OVA攻击后导致嗜酸性肺部炎症。这种表型部分逆转的干扰素γ（IFN-γ）或IL-17的情况下。结论金黄色葡萄球菌EV可诱导Th1和Th17细胞的肺部炎症反应，且以TLR2依赖性为主。此外，S.金黄色葡萄球菌EV增强气道对吸入性变应原的超敏反应的发展。
Background Recent evidence indicates that Staphylococcus aureus, one of the most important human pathogens, secretes vesicles into the extracellular milieu. Objective To evaluate whether inhalation of S. aureus-derived extracellular vesicles (EV) is causally related to the pathogenesis of inflammatory pulmonary diseases. Methods Staphylococcus aureus EV were prepared by sequential ultrafiltration and ultracentrifugation. The innate immune response was evaluated in vitro after the application of EV to airway epithelial cells and alveolar macrophages. In vivo innate and adaptive immune responses were evaluated after airway exposure to EV. Adjuvant effects of EV on the development of hypersensitivity to inhaled allergens were also evaluated after airway sensitization with S. aureus EV and ovalbumin (OVA). Results Staphylococcus aureus and S. aureus EV were detected in house dust. Alveolar macrophages produced both tumor necrosis alpha (TNF-alpha) and interleukin 6 (IL-6) after in vitro stimulation with S. aureus EV, whereas airway epithelial cells produced only IL-6. Repeated airway exposure to S. aureus EV induced both Th1 and Th17 cell responses and neutrophilic pulmonary inflammation, mainly via a Toll-like receptor 2 (TLR2)-dependent mechanism. In terms of adjuvant effects, airway sensitization with S. aureus EV and OVA resulted in neutrophilic pulmonary inflammation after OVA challenge alone. This phenotype was partly reversed by the absence of interferon gamma (IFN-gamma) or IL-17. Conclusion Staphylococcus aureus EV can induce Th1 and Th17 neutrophilic pulmonary inflammation, mainly in a TLR2-dependent manner. Additionally, S. aureus EV enhance the development of airway hypersensitivity to inhaled allergens.