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Evolutionary and functional relationships of cytokines expressed by the helminth Echinococcus multilocularis and its mammalian host

Fachliche Zuordnung Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
Förderung Förderung von 2010 bis 2015
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 180451182
 
Parasitic helminths induce long-lasting, chronic infections associated with Th2-biased immune responses and strong immunosuppressive effects, elicited by regulatory T cells and alternatively activated macrophages through the secretion of cytokines like IL-10 and TGF-β. As metazoans, helminths are closely related to their mammalian hosts and utilize evolutionary conserved cytokines for cell-cell-communication that are also involved in regulating innate and adaptive immune responses in mammals. The present project investigates whether parasitic helminths utilize evolutionary conserved cytokines to interfere with the anti-parasitic immune response and to alter host cell physiology at the site of infection. As a model, we use the larval stage of the tapeworm Echinococcus multilocularis for which we have developed sophisticated in vitro cultivation systems, initiated a genome sequencing project, and characterized several evolutionary conserved cytokines, in particular of the TGF-β/BMP-family. This project first aims to functionally express the parasite’s TGF-β/BMP-orthologs in mammalian expression systems and to study their interaction with corresponding surface receptors of the TGF-β/BMP-receptor families of the host. Based on the identified activation patterns, in vitro assays to study the effects of parasite-derived cytokines from early and late stages of the infection on the activation of immune-effector cells and cells of the liver, the primary site of infection, will be established.
DFG-Verfahren Sachbeihilfen
 
 

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