Hyper-IgE syndromes: key to understand Staphylococcus aureus immune defense and associated allergy

尽管进行了深入的研究，但关于宿主对金黄色葡萄球菌的防御及其对过敏性疾病的影响仍然存在很多问题。S.金黄色葡萄球菌感染和变应性疾病的稳步上升是世界范围内的政治卫生保健问题。高IgE综合征（HIES）是一种原发性免疫缺陷综合征，与以复发性S。金黄色皮肤和呼吸道感染，湿疹和血清IgE升高。针对STAT 3基因突变引起的常染色体显性遗传HIES，我们希望了解S。金黄色葡萄球菌毒力因子、特异性S.金黄色葡萄球菌IgG和IgE以及宿主防御S.金黄色。因此，S。金黄色葡萄球菌病原体和毒素将从特应性皮炎和HIES患者中分离，表征，并与临床和免疫学表现如特异性抗体产生相关。在S.金黄色葡萄球菌的免疫防御和过敏性疾病目前还没有很好的理解。重点放在STAT 3信号通路，我们将评估HIES和特应性皮炎患者的原代上皮细胞与健康对照和遗传修饰的上皮细胞模型的物理上皮屏障，抗菌因子的调节，和Th细胞分化后暴露于S。金黄色。此外，将评估Th 2-或Th 17-细胞环境的影响。我们期望获得关于STAT 3-IL 17轴在抗S.以及如何有益地影响这个轴。

There are still lots of questions in regards to host defense against Staphylococcus aureus and its impact on allergic disease despite intensive research. Antibiotic resistance of S. aureus infections and a steady rise of allergic diseases are political health care issues world-wide. Hyper-IgE syndromes (HIES) are primary immunodeficiencies which overlap with severe forms of atopic dermatitis presenting with recurrent S. aureus skin and respiratory infections, eczema and elevated serum-IgE. Focused on autosomal dominant HIES which is caused by mutations in the gene STAT3, we want to understand the role of S. aureus virulence factors, specific S. aureus IgG and IgE, and the epithelium in host defense against S. aureus. Therefore S. aureus pathogens and toxins will be isolated from atopic dermatitis and HIES patients, characterized, and correlated to the clinical and immunological presentation such as specific antibody production. The contribution of the epithelium in in S. aureus immune defense and allergic diseases is currently not well understood. Focused on the STAT3 signaling pathway we will assess primary epithelial cells of HIES and atopic dermatitis patients versus healthy controls and genetically modified epithelial cell models regarding physical epithelial barrier, regulation of antimicrobial factors, and Th cell differentiation after exposure to S. aureus. Furthermore, the influence of a Th2- or Th17-cell milieu will be assessed. We expect to obtain detailed information about the role of the STAT3-IL17 axis in immunity against S. aureus and how to beneficially influence this axis.