Host insulin stimulates Echinococcus multilocularisinsulin signalling pathways and larval development

BMC Biology

Research Article

Thomas Dandekar¹  Dominik Schaack¹  Andrew Hemphill²  Britta Stadelmann²  Markus Spiliotis³  Klaus Brehm³  Sabine Förster³  Verena Gelmedin³  Christian Konrad³  Sarah Hemer³  Uriel Koziol³ 

[1] Department of Bioinformatics, University of Würzburg, Biocenter am Hubland, D-97074, Würzburg, Germany;Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012, Bern, Switzerland;University of Würzburg, Institute of Hygiene and Microbiology, Josef-Schneider-Strasse 2, D-97080, Würzburg, Germany;

关键词: Cestode;    Tapeworm;    Echinococcus;    Echinococcosis;    Insulin;    Receptor kinase;    Kinase inhibitor;    Host-parasite interaction;   

DOI  :  10.1186/1741-7007-12-5

 received in 2013-11-18, accepted in 2014-01-21,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe metacestode of the tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal zoonosis. Infections are initiated through establishment of parasite larvae within the intermediate host’s liver, where high concentrations of insulin are present, followed by tumour-like growth of the metacestode in host organs. The molecular mechanisms determining the organ tropism of E. multilocularis or the influences of host hormones on parasite proliferation are poorly understood.ResultsUsing in vitro cultivation systems for parasite larvae we show that physiological concentrations (10 nM) of human insulin significantly stimulate the formation of metacestode larvae from parasite stem cells and promote asexual growth of the metacestode. Addition of human insulin to parasite larvae led to increased glucose uptake and enhanced phosphorylation of Echinococcus insulin signalling components, including an insulin receptor-like kinase, EmIR1, for which we demonstrate predominant expression in the parasite’s glycogen storage cells. We also characterized a second insulin receptor family member, EmIR2, and demonstrated interaction of its ligand binding domain with human insulin in the yeast two-hybrid system. Addition of an insulin receptor inhibitor resulted in metacestode killing, prevented metacestode development from parasite stem cells, and impaired the activation of insulin signalling pathways through host insulin.ConclusionsOur data indicate that host insulin acts as a stimulant for parasite development within the host liver and that E. multilocularis senses the host hormone through an evolutionarily conserved insulin signalling pathway. Hormonal host-parasite cross-communication, facilitated by the relatively close phylogenetic relationship between E. multilocularis and its mammalian hosts, thus appears to be important in the pathology of alveolar echinococcosis. This contributes to a closer understanding of organ tropism and parasite persistence in larval cestode infections. Furthermore, our data show that Echinococcus insulin signalling pathways are promising targets for the development of novel drugs.

【 授权许可】

Unknown   
© Hemer et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.