Dysregulation der WNT/Beta-catenin-Signalachse bei chronischer endothelialer Infektion

细胞内的肺炎衣原体通过单核细胞传播到血管内皮细胞，在那里它会引起与动脉粥样硬化相关的频繁的慢性感染。在内皮细胞中，它以复制状态存在，导致内皮破坏，并以非复制状态存在，导致慢性感染。根据我们建立的衣原体持久性模型，我们推测血管内皮细胞通过两种机制诱导衣原体持久性：1.参与氨基酸代谢的酶(TrpB/P，AsPC)转录改变，损害衣原体营养库。2.蛋白质合成减少(INCA/B/C)，提供衣原体包涵体膜的完整性，或其分泌被衣原体III型机械破坏，导致具有持久性特征的结构异常的包涵体。结果，衣原体HSP60表达上调，继而引发促炎内皮细胞表达谱。这些衣原体靶基因的转录活性和蛋白表达将利用原代细胞和允许感染从单核细胞传播到内皮细胞的跨内皮细胞迁移模型来分析持续和活跃的人血管内皮细胞。在体内，将在慢性血管内皮细胞感染的小鼠模型中分析持久性。

The intracellular bacterium Chlamydia pneumoniae is spread by blood monocytes to the vascular endothelium where it causes a frequent chronic infection related to atherosclerosis. In the endothelium it exists in a replicative state leading to endothelial destruction and in a non-replicative state leading to chronic infection. Based on models of persistence established by us, we postulate that the endothelium itself induces chlamydial persistence by two mechanisms: 1. Altered transcription for enzymes involved in amino acid metabolism (TrpB/P, AspC) impairs chlamydial nutrient pools. 2. Decreased synthesis of proteins (IncA/B/C), providing the integrity of the chlamydial inclusion membrane, or their impaired secretion by the chlamydial type III machinery result in the structurally aberrant inclusion bodies characteristic of persistence. As a result chlamydial HSP 60 is upregulated, which then provokes a proinflammatory endothelial expression profile. The transcriptional activity of these chlamydial target genes and the protein expression will be analysed in persistently and actively infected human vascular endothelium using primary cells and a model of transendothelial migration, which permits transmission of the infection from monocytes to endothelium. In vivo, persistence will be analysed in a mouse model of chronic vascular endothelial infection.