TLR2 activation underlying immune regulation at interfaces

• Antragsteller: Professor Dr. Tilo Biedermann; Professor Dr. Friedrich Götz
• Fachliche Zuordnung: Immunologie
• Förderung: Förderung von 2011 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 212173602

Innate immune signals mediate pro-, anti-inflammatory and/or tolerogenic responses. We identified TLR2 activation as important pathway to induce IL 10 production, regulatory T cells and to suppress atopic dermatitis in both humans and mouse models. Functional analyses of TLR2 ligands revealed that cutaneous application of di-acylated Pam2Cys, but not of tri-acylated Pam3Cys, inhibited subsequent cutaneous inflammation, and IgE and IgG1 responses. These findings indicate that immune modulation is mediated by TLR2-TLR6 ligands (Pam2Cys) but not by TLR1-TLR2 ligands (Pam3Cys). Whether natural lipoproteins of Staphylococcus aureus are di- or tri-acylated is still controversial. We hypothesize that in pathogenic species the lipid moiety of lipoproteins is tri-acylated, because of the additional N-acylation, and in non-pathogenic (commensal) staphylococci these are only di-acylated. With our approach, we hope to find an answer to one of the central questions in immunology, why commensal bacteria on our skin are more easily tolerated by the immune system while pathogenic species readily induce inflammation.

• DFG-Verfahren: Sachbeihilfen