Cytokine induction by Gram-positive bacteria

尽管革兰氏阳性和革兰氏阴性感染具有相似的临床相关性，但迄今为止，人们对革兰氏阳性细菌的免疫激活作用的了解远远少于对革兰氏阴性细菌的免疫激活作用。我们小组已经将高纯度脂磷壁酸(LTA)作为革兰氏阳性免疫刺激的关键成分。该项目的第一阶段确定了LTA效力低于革兰氏阴性脂多糖(LPS)的原因，确定缺乏IL-12/IFNy诱导是TLR2激动剂的一般特征，以及需要将LTA呈现在表面以增强免疫刺激效力。第二阶段涉及趋化因子诱导的各个方面，其中LTA比脂多糖更有效，并进一步描述了LTA呈现的现象。此外，在SPP 1110的合作中，发现了新的补体和植物防御激活以及CD36作为一种新的LTA受体。最后的项目阶段将解决细菌共刺激分子和LTA可诱导反应的调节器：从迄今16个细菌物种中分离的LTA，尽管结构不同，但行为非常相似，而整个活细菌和被杀死的细菌在诱导反应模式方面不同。应对细菌细胞壁的各个成分进行提纯和表征。

Despite similar clinical relevance of Gram-positive and Gram-negative infection, immune activation by Gram-positive bacteria is by far less well understood than immune activation by Gram-negative bacteria. Our group has made available highlypurified lipoteichoic acids (LTA) as a key Gram-positive immune stimulatory component. The first phase of the project characterised the reasons for lower potency of LTA compared to Gram-negative lipopolysaccharide (LPS) identifying lack of IL-12/IFNy induction as a general characteristic of TLR2 agonists and need for presentation of LTA on surfaces for enhanced immunostimulatory potency as major aspects. The second phase addressed aspects of chemokine induction, where LTA is more potent than LPS, and further characterized the phenomenon of LTA presentation. Furthermore, within collaborations of SPP 1110, novel complement and plant defence activation as well as CD36 as a new LTA receptor were identified. The final project phase shall address the bacterial costimuli and modulators of LTA inducible responses: LTA isolated from so far 16 bacterial species, although different in structure, behave remarkably similar while whole live and killed bacteria differ with regard to the pattern of induced responses. The respective components of the bacterial cell wall shall be purified and characterised.