Host insulin stimulates Echinococcus multilocularis insulin signalling pathways and larval development

BMC Biology
Sarah HemerKlaus Brehm

Abstract

The 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. Using 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...Continue Reading

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Citations

Nov 5, 2015·The New England Journal of Medicine·Atis MuehlenbachsSherif R Zaki
Aug 25, 2015·Veterinary Parasitology·U Koziol, K Brehm
Feb 7, 2015·Parasites & Vectors·Natalia MacchiaroliMara Cecilia Rosenzvit
Dec 20, 2014·Parasite : Journal De La Société Française De Parasitologie·Klaus Brehm, Uriel Koziol
Oct 23, 2016·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Yan-Lei FanWan-Zhong Jia
Jul 9, 2016·International Journal for Parasitology·Uriel KoziolEstela Castillo
Apr 27, 2017·Journal of Proteomics·Karina M MonteiroHenrique B Ferreira
Dec 28, 2019·PLoS Neglected Tropical Diseases·Matías Gastón PérezMara Cecilia Rosenzvit
Jun 17, 2020·Antimicrobial Agents and Chemotherapy·Julia A LoosAndrea C Cumino
Feb 15, 2019·Clinical Microbiology Reviews·Hao WenDonald P McManus
May 28, 2020·Frontiers in Immunology·Justin Komguep NonoKlaus Brehm
Mar 23, 2021·PLoS Neglected Tropical Diseases·Natalia MacchiaroliMara Cecilia Rosenzvit
Jun 10, 2021·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Shadike ApaerTuerhongjiang Tuxun

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Datasets Mentioned

BETA
HF934006

Methods Mentioned

BETA
two-hybrid
ELISA
PCR
immunoprecipitation
electron microscopy
transmission electron microscopy
electrophoresis
two hybrid
FCS
PCRs

Software Mentioned

Simple Modular Architecture Research Tool ( SMART )
Basic Local Alignment Search Tool ( BLAST )
JAVA
PRO
Openlab
Basic Local Alignment Search Tool
Simple Modular Architecture Research Tool
SMART
BLAST

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