Charakterisierung von antimikrobiellen Effektormechanismen in humanen Endothelzellen nach Stimulation mit Interferon

• Applicant: Professor Dr. Walter Däubener
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2002 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5388644

The endothelium plays an important role in the pathophysiology of many infectious diseases either as a target organ or by acting as a barrier/portal of entry for the invading organisms. We have recently shown that human brain microvascular endothelial cells (HBMEC) are capable of restricting bacterial (staphylococci and streptococci), parasitic (toxoplasma) and viral (HSV, CMV) growth after stimulation with IFN-g. We found that in all cases IFN-g induced activation of the tryptophan degrading enzyme indoleamine 2,3-dioxygenase is responsible for the anti-pathogen effect. The pathogens mentioned above are important causes of morbidity and mortality in both adults and neonates. Especially in the case of CMV endothelial cells are major target cells. In our study we intend comparing the anti-viral effect of interferon activated endothelial cells derived from the umbilical vein (HUVEC) with that mediated by human brain microvascular endothelial cells (HBMEC). It is known that the two endothelial cell lines HBMEC and HUVEC utilize different anti-pathogen effector-mechanisms. We will analyze whether this is due to tissue specific endothelial differentiation or due to the developmental age (newborn vs. adult). We will focus our interest especially on the comparison of the anti-viral effector-mechanisms induced by type I and type II interferons, the role of nitric oxide produced by endothelial cells on IDO activity and in regulatory steps involved in IDO induction in different cells. Furthermore we want to define whether or not the influence of CMV infection on the IFN-signaling cascade is sufficient to inhibit antiviral effects mediated by interferons in endothelial cells.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1130: Infections of the Endothelium
• Participating Person: Professor Dr. Horst Schroten