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

• Applicant: Professor Dr. Matthias Maaß
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2002 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5389455

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.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1130: Infections of the Endothelium
• International Connection: Austria