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Introduction: Arcobacter butzleri is considered an emerging zoonotic pathogen. Although no obvious effects on animal health (pigs and poultry) have been reported, severe gastroenteritis can occur in human. However, the molecular mechanisms of the innate immune
response to A. butzleri remain poorly understood. The aim of th is project is to generate basic knowledge of molecular interactions upon infection. Identification of virulence factors as well as involved key regulators such as microRNAs will help us to evaluate the pathogenicity of the disease. Based on this knowledge we will be able to develop alternative therapeutic strategies to combat the pathogen.
Material and Methods: To evaluate the influence of A. butzleri on macrophages different strains were studied in an in vitro infection model using THP-1 cells. Custom RT-qPCR arrays were used to investigate mRNA expression levels. Apoptosis assays were performed to reveal the ability of A. butzleri to influence macrophage host response. microRNA specific RT-qPCR arrays were used to study the expression of predicted microRNAs regulating the apoptotic pathway.
Results: The expression of pro-inflammatory cytokines typically produced in macro phages was highly induced. The apoptotic marker Caspase 8 was induced in early stages of infection. Interestingly, the mRNA expression of Caspase 8 was down regulated by A. butzleri whereas a potential interacting microRNA showed increased expression compared with the non infected control. Current attempts are directed towards the potential role of TNF in this context.
Conclusions: The current study will help to gain insight into the molecular mechanisms of host-pathogen-interaction enabling the generation of future strategies to target A. butzleri induced diseases.
The study was supported by grants from DFG (SFB 852 project B4)