TLR2 activation underlying immune regulation at interfaces

先天免疫信号介导促、抗炎和/或耐受性反应。在人和小鼠模型中，我们发现TLR2激活是诱导IL - 10生成、调节性T细胞和抑制特应性皮炎的重要途径。TLR2配体的功能分析显示，皮肤应用二酰化Pam2Cys，而非三酰化Pam3Cys，可以抑制随后的皮肤炎症以及IgE和IgG1反应。这些发现表明免疫调节是由TLR2-TLR6配体（Pam2Cys）介导的，而不是由TLR1-TLR2配体（Pam3Cys）介导的。金黄色葡萄球菌的天然脂蛋白是二酰化还是三酰化仍有争议。我们假设，在致病性葡萄球菌中，由于额外的n-酰化，脂蛋白的脂质部分是三酰化的，而在非致病性（共生）葡萄球菌中，这些只是二酰化的。通过我们的方法，我们希望找到免疫学中一个核心问题的答案，为什么我们皮肤上的共生细菌更容易被免疫系统耐受，而致病细菌却很容易引起炎症。

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.