The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction
Background 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 mech...
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| Sprog: | engelsk |
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2019
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| Online adgang: | https://hdl.handle.net/20.500.12008/28106 |
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| _version_ | 1868890064544595968 |
|---|---|
| author | Forster, S. C. |
| author2 | Koziol, Uriel Schafe, T. Duvoisin, R. Cailliau, K. Vanderstraete, M. Dissous, C. Brehm, Klaus |
| author2_role | author author author author author author author |
| author_browse | Brehm, Klaus Cailliau, K. Dissous, C. Duvoisin, R. Forster, S. C. Koziol, Uriel Schafe, T. Vanderstraete, M. |
| author_facet | Forster, S. C. Koziol, Uriel Schafe, T. Duvoisin, R. Cailliau, K. Vanderstraete, M. Dissous, C. Brehm, Klaus |
| author_role | author |
| collection | COLIBRI |
| dc.contributor.none.fl_str_mv | Forster S. C. Koziol Uriel, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología. Schafe T. Duvoisin R. Cailliau K. Vanderstraete M. Dissous C. Brehm K. |
| dc.creator.none.fl_str_mv | Forster, S. C. Koziol, Uriel Schafe, T. Duvoisin, R. Cailliau, K. Vanderstraete, M. Dissous, C. Brehm, Klaus |
| dc.date.none.fl_str_mv | 2019 2021-06-08T13:38:11Z 2021-06-08T13:38:11Z |
| dc.format.none.fl_str_mv | 27 h. application/pdf |
| dc.identifier.none.fl_str_mv | Forster, S, Koziol, U, Schafe, T, [y otros] "The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction". PLoS Neglected Tropical Diseases. [en línea] 2019, 13(3): e0006959. 27 h. DOI: 10.137/journal.pntd.0006959 1935-2735 https://hdl.handle.net/20.500.12008/28106 10.1371/journal.pntd.0006959 |
| dc.language.none.fl_str_mv | en eng |
| dc.publisher.none.fl_str_mv | Public Library of Science |
| dc.relation.none.fl_str_mv | PLoS Neglected Tropical Diseases, 2019, 13(3): e0006959 |
| dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess Licencia Creative Commons Atribución (CC - By 4.0) |
| dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
| dc.subject.none.fl_str_mv | Echinococcus multilocularis Fibroblast growth factor Host-parasite interaction |
| dc.title.none.fl_str_mv | The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | Background 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. Methodology/Principal findings 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 survival of metacestode vesicles and parasite stem cells were drastically affected in vitro in the presence of BIBF 1120. Conclusions/Significance Our data indicate that mammalian FGF, which is present in the liver and upregulated during fibrosis, supports the establishment of the Echinococcus metacestode during AE by acting on an evolutionarily conserved parasite FGF signalling system. These data are valuable for understanding molecular mechanisms of organ tropism and host-parasite interaction in AE. Furthermore, our data indicate that the parasite’s FGF signalling systems are promising targets for the development of novel drugs against AE. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_57393f80f8efe25cdca3d2f2fcff7ae5 |
| identifier_str_mv | Forster, S, Koziol, U, Schafe, T, [y otros] "The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction". PLoS Neglected Tropical Diseases. [en línea] 2019, 13(3): e0006959. 27 h. DOI: 10.137/journal.pntd.0006959 1935-2735 10.1371/journal.pntd.0006959 |
| instacron_str | Universidad de la República |
| institution | Universidad de la República |
| instname_str | Universidad de la República |
| language | eng |
| language_invalid_str_mv | en |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/28106 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher.none.fl_str_mv | Public Library of Science |
| reponame_str | COLIBRI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
| spelling | The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interactionForster, S. C.Koziol, UrielSchafe, T.Duvoisin, R.Cailliau, K.Vanderstraete, M.Dissous, C.Brehm, KlausEchinococcus multilocularisFibroblast growth factorHost-parasite interactionBackground 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. Methodology/Principal findings 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 survival of metacestode vesicles and parasite stem cells were drastically affected in vitro in the presence of BIBF 1120. Conclusions/Significance Our data indicate that mammalian FGF, which is present in the liver and upregulated during fibrosis, supports the establishment of the Echinococcus metacestode during AE by acting on an evolutionarily conserved parasite FGF signalling system. These data are valuable for understanding molecular mechanisms of organ tropism and host-parasite interaction in AE. Furthermore, our data indicate that the parasite’s FGF signalling systems are promising targets for the development of novel drugs against AE.Public Library of ScienceForster S. C.Koziol Uriel, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.Schafe T.Duvoisin R.Cailliau K.Vanderstraete M.Dissous C.Brehm K.2021-06-08T13:38:11Z2021-06-08T13:38:11Z2019Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion27 h.application/pdfForster, S, Koziol, U, Schafe, T, [y otros] "The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction". PLoS Neglected Tropical Diseases. [en línea] 2019, 13(3): e0006959. 27 h. DOI: 10.137/journal.pntd.00069591935-2735https://hdl.handle.net/20.500.12008/2810610.1371/journal.pntd.0006959reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengPLoS Neglected Tropical Diseases, 2019, 13(3): e0006959Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/281062026-04-14T10:09:39Z |
| spellingShingle | The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction Forster, S. C. Echinococcus multilocularis Fibroblast growth factor Host-parasite interaction |
| status_str | publishedVersion |
| title | The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction |
| title_full | The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction |
| title_fullStr | The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction |
| title_full_unstemmed | The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction |
| title_short | The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction |
| title_sort | The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction |
| topic | Echinococcus multilocularis Fibroblast growth factor Host-parasite interaction |
| url | https://hdl.handle.net/20.500.12008/28106 |