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来源于农场的革兰氏阳性菌藤黄微球菌 W620 可预防 HDM 和 OVA 暴露的小鼠发生哮喘表型。

Farm-derived Gram-positive bacterium Staphylococcus sciuri W620 prevents asthma phenotype in HDM- and OVA-exposed mice.

机构信息

Institute for Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Marburg, Germany.

出版信息

Allergy. 2013 Mar;68(3):322-9. doi: 10.1111/all.12094. Epub 2013 Feb 1.

Abstract

BACKGROUND

Farm-derived dust samples have been screened for bacteria with potential allergo-protective properties. Among those was Staphylococcus sciuri W620 (S. sciuri W620), which we tested with regard to its protective capacities in murine models of allergic airway inflammation.

METHODS

We employed two protocols of acute airway inflammation in mice administering either ovalbumin (OVA) or house dust mite extract (HDM) for sensitization. Mechanistic studies on the activation of innate immune responses to S. sciuri W620 were carried out using human primary monocytic dendritic cells (moDC) and co-culture with autologous T cells.

RESULTS

The allergo-protective properties of S. sciuri W620 were proven in a T(H)2-driven OVA model as well as in a mixed T(H)1/T(H)2 phenotype HDM model as demonstrated by abrogation of eosinophils and neutrophils in the airways after intranasal treatment. In the HDM model, lymph node cell T(H)1/T(H)2 signature cytokines were decreased in parallel. Studies on human moDC revealed an activation of TLR2 and NOD2 receptors and initiation of DC maturation following incubation with S. sciuri W620. Cytokine expression analyses after exposure to S. sciuri W620 showed a lack of IL-12 production in moDC due to missing transcription of the IL-12p35 mRNA. However, such DC selectively supported T(H)1 cytokine release by co-cultured T cells.

CONCLUSION AND CLINICAL RELEVANCE

Our proof-of-concept experiments verify the screening system of farm-derived dust samples as suitable to elucidate new candidates for allergo-protection. S. sciuri W620 was shown to possess preventive properties on airway inflammation providing the basis for further mechanistic studies and potential clinical implication.

摘要

背景

从农场衍生的灰尘样本中筛选出具有潜在变应原保护特性的细菌。其中包括金黄色葡萄球菌 W620(S. sciuri W620),我们测试了它在变应性气道炎症的小鼠模型中的保护能力。

方法

我们采用两种急性气道炎症模型,用卵清蛋白(OVA)或屋尘螨提取物(HDM)对小鼠进行致敏。使用人原代单核细胞树突状细胞(moDC)和与自体 T 细胞共培养,研究 S. sciuri W620 对固有免疫反应的激活机制。

结果

S. sciuri W620 在 T(H)2 驱动的 OVA 模型以及混合 T(H)1/T(H)2 表型 HDM 模型中表现出变应原保护特性,表现为经鼻治疗后气道中的嗜酸性粒细胞和中性粒细胞减少。在 HDM 模型中,淋巴结细胞 T(H)1/T(H)2 特征细胞因子平行减少。对人 moDC 的研究表明,S. sciuri W620 孵育后 TLR2 和 NOD2 受体被激活,并启动 DC 成熟。暴露于 S. sciuri W620 后的细胞因子表达分析表明,由于 IL-12p35 mRNA 的转录缺失,moDC 中缺乏 IL-12 的产生。然而,这样的 DC 选择性地支持共培养的 T 细胞释放 T(H)1 细胞因子。

结论和临床相关性

我们的概念验证实验验证了从农场衍生的灰尘样本筛选系统适合阐明新的变应原保护候选物。S. sciuri W620 具有预防气道炎症的特性,为进一步的机制研究和潜在的临床应用提供了基础。

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