The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction

PLoS Neglected Tropical Diseases
Sabine FörsterKlaus Brehm

Abstract

Alveolar echinococcosis (AE) is a lethal zoonosis caused by the metacestode larva of the tapeworm Echinococcus multilocularis. The infection is characterized by tumour-like growth of the metacestode within the host liver, leading to extensive fibrosis and organ-failure. The molecular mechanisms of parasite organ tropism towards the liver and influences of liver cytokines and hormones on parasite development are little studied to date. We show that the E. multilocularis larval stage expresses three members of the fibroblast growth factor (FGF) receptor family with homology to human FGF receptors. Using the Xenopus expression system we demonstrate that all three Echinococcus FGF receptors are activated in response to human acidic and basic FGF, which are present in the liver. In all three cases, activation could be prevented by addition of the tyrosine kinase (TK) inhibitor BIBF 1120, which is used to treat human cancer. At physiological concentrations, acidic and basic FGF significantly stimulated the formation of metacestode vesicles from parasite stem cells in vitro and supported metacestode growth. Furthermore, the parasite's mitogen activated protein kinase signalling system was stimulated upon addition of human FGF. The sur...Continue Reading

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Citations

Dec 28, 2019·PLoS Neglected Tropical Diseases·Matías Gastón PérezMara Cecilia Rosenzvit
Jun 17, 2020·Antimicrobial Agents and Chemotherapy·Julia A LoosAndrea C Cumino
Aug 15, 2019·Diseases·Fuqiu NiuYumin Zhao
May 28, 2020·Frontiers in Immunology·Justin Komguep NonoKlaus Brehm
Mar 23, 2021·PLoS Neglected Tropical Diseases·Natalia MacchiaroliMara Cecilia Rosenzvit
Mar 23, 2021·Frontiers in Immunology·Hong YouDonald P McManus

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Datasets Mentioned

BETA
LT599044
LT599045
LT599046

Methods Mentioned

BETA
X-ray
PCR
ELISA
in vitro transcription
FCS
reverse transcription PCR
WMISH

Software Mentioned

BLAST
StepOne
BLASTP
TBLASTN
PROT
SMART ( Simple Modular Architecture Tool )
GraphPad Prism
DNASTAR
PROT BLASTP
SWISS

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