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

屋尘螨 免疫学 树突状细胞 卵清蛋白 TLR2型 细胞因子 免疫系统 生物 医学 先天免疫系统 化学 过敏原 过敏
作者
Stefanie Hagner,Hani Harb,Min Zhao,Karina Stein,Otto Holst,Markus Ege,Melanie Mayer,Jakob Matthes,Johann Bauer,Erika von Mutius,H. Renz,Holger Heine,Petra Ina Pfefferle,Holger Garn
出处
期刊:Allergy [Wiley]
卷期号:68 (3): 322-329 被引量:68
标识
DOI:10.1111/all.12094
摘要

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.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.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.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.
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