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

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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.