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Contrasting immunological effects of two disparate dusts - preliminary observations.

机译:两种不同粉尘的对比免疫学作用-初步观察。

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BACKGROUND: Modern lifestyle and urbanization have been associated with a raised risk for atopic diseases whereas early and long-term exposure to a farm environment confers protection against atopic sensitization. Immunomodulatory potential and microbiological characteristics of settled airborne dust from an urban house and a barn were examined. METHODS: Pulmonary inflammation was induced in mice by repeated intranasal administration of dusts. Monocyte-derived human dendritic cells (moDCs) were exposed to dusts followed by coculture with purified naive T cells. Cytokine/chemokine mRNA and protein levels were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry. The dusts were analyzed by cloning and sequencing of 16S rRNA genes (290 sequences) for DNA, lipids, endotoxin and beta-glucan, by live-dead staining, viable counting, isolation and identification of pure cultures (n = 76). RESULTS: Repeated exposure to house dust elicited pulmonary eosinophilia in mice whereas exposure to barn dust elicited neutrophilic and lymphocytic airway inflammation. Stimulation of moDCs with urban house dust elicited expression of Th2-promoting OX40L and Jagged-1 costimulatory molecules. Dendritic cells (DCs) exposed to house dust directed naive T cells towards Th2 responses. Exposure of DCs to barn dust elicited the development of Th1-dominated immune responses. Urban house dust contained bacterial debris almost exclusively of human commensal species (corynebacteria, streptococci) whereas barn dust comprised mainly intact, viable bacteria of high diversity and no commensal species. CONCLUSION: Contact to debris originating from human commensal bacteria in urban house dust elicited a Th2-type response whereas barn dust with high bacterial diversity directed the cells towards a Th1 response.
机译:背景:现代生活方式和城市化与特应性疾病的风险增加有关,而早期和长期暴露于农场环境可防止特应性过敏。检查了城市房屋和谷仓中沉降的悬浮尘埃的免疫调节潜力和微生物学特征。方法:反复鼻内施用粉尘可引起小鼠肺部炎症。将单核细胞衍生的人树突细胞(moDC)暴露于尘土,然后与纯化的天然T细胞共培养。通过实时聚合酶链反应,酶联免疫吸附测定和流式细胞仪分析细胞因子/趋化因子的mRNA和蛋白水平。通过对16S rRNA基因(290个序列)的克隆,测序,活菌染色,活菌计数,纯培养物的分离和鉴定(n = 76),对尘埃进行了分析,并对DNA,脂质,内毒素和β-葡聚糖进行了测序。结果:反复暴露于室内灰尘会引起小鼠肺嗜酸性粒细胞增多,而暴露于谷仓灰尘会引起嗜中性和淋巴细胞气道炎症。用城市房屋尘埃刺激moDCs会诱导Th2促进OX40L和Jagged-1共刺激分子的表达。暴露于尘土中的树突状细胞(DC)将幼稚T细胞导向Th2反应。 DC暴露于谷仓粉尘中引发了以Th1为主的免疫反应的发展。城市房屋的灰尘几乎只包含人类共生物种(棒状杆菌,链球菌)的细菌碎片,而谷仓的灰尘则主要包括完整的,具有高度多样性的存活细菌,没有共生物种。结论:接触城市房屋尘埃中人类共生细菌的碎片会引发Th2型应答,而具有高细菌多样性的谷仓尘埃则使细胞趋向于Th1型应答。

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