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

• Applicant: Professor Dr. Klaus Brehm
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 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 Programme: Research Grants