Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode
Resumen:
The lethal zoonosis alveolar echinococcosis (AE) is caused by tumor-like, infiltrative growth of the metacestode larval stage of the tapeworm Echinococcus multilocularis. We previously showed that the metacestode is composed of posteriorized tissue and that the production of the subsequent larval stage, the protoscolex, depends on re-establishment of anterior identities within the metacestode germinative layer. It is, however, unclear so far how protoscolex differentiation in Echinococcus is regulated. We herein characterized the full complement of E. multilocularis TGFb/BMP receptors, which is composed of one type II and three type I receptor serine/threonine kinases. Functional analyzes showed that all Echinococcus TGFb/BMP receptors are enzymatically active and respond to host derived TGFb/BMP ligands for activating downstream Smad transcription factors. In situ hybridization experiments demonstrated that the Echinococcus TGFb/BMP receptors are mainly expressed by nerve and muscle cells within the germinative layer and in developing brood capsules. Interestingly, the production of brood capsules, which later give rise to protoscoleces, was strongly suppressed in the presence of inhibitors directed against TGFb/BMP receptors, whereas protoscolex differentiation was accelerated in response to host BMP2 and TGFb. Apart from being responsive to host TGFb/BMP ligands, protoscolex production also correlated with the expression of a parasite-derived TGFb-like ligand, EmACT, which is expressed in early brood capsules and which is strongly expressed in anterior domains during protoscolex development. Taken together, these data indicate an important role of TGFb/BMP signalling in Echinococcus anterior pole formation and protoscolex development. Since TGFb is accumulating around metacestode lesions at later stages of the infection, the host immune response could thus serve as a signal by which the parasite senses the time point at which protoscoleces must be produced. Overall, our data shed new light on molecular mechanisms of host-parasite interaction during AE and are relevant for the development of novel treatment strategies.
2023 | |
Echinococcosis TGFb BMP Protoscolex Brood capsulet Differentiation Body axes Development |
|
Inglés | |
Universidad de la República | |
COLIBRI | |
https://hdl.handle.net/20.500.12008/43232 | |
Acceso abierto | |
Licencia Creative Commons Atribución (CC - By 4.0) |
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author | Kaethner, Marc |
author2 | Epping, Kerstin Bernthaler, Peter Rudolf, Kilian Thomann, Irena Leitschuh, Nadine Bergmann, Monika Spiliotis, Markus Koziol, Uriel Brehm, Klaus |
author2_role | author author author author author author author author author |
author_facet | Kaethner, Marc Epping, Kerstin Bernthaler, Peter Rudolf, Kilian Thomann, Irena Leitschuh, Nadine Bergmann, Monika Spiliotis, Markus Koziol, Uriel Brehm, Klaus |
author_role | author |
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collection | COLIBRI |
dc.contributor.filiacion.none.fl_str_mv | Kaethner Marc Epping Kerstin Bernthaler Peter Rudolf Kilian Thomann Irena Leitschuh Nadine Bergmann Monika Spiliotis Markus Koziol Uriel, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología. Brehm Klaus |
dc.creator.none.fl_str_mv | Kaethner, Marc Epping, Kerstin Bernthaler, Peter Rudolf, Kilian Thomann, Irena Leitschuh, Nadine Bergmann, Monika Spiliotis, Markus Koziol, Uriel Brehm, Klaus |
dc.date.accessioned.none.fl_str_mv | 2024-03-20T13:54:27Z |
dc.date.available.none.fl_str_mv | 2024-03-20T13:54:27Z |
dc.date.issued.none.fl_str_mv | 2023 |
dc.description.abstract.none.fl_txt_mv | The lethal zoonosis alveolar echinococcosis (AE) is caused by tumor-like, infiltrative growth of the metacestode larval stage of the tapeworm Echinococcus multilocularis. We previously showed that the metacestode is composed of posteriorized tissue and that the production of the subsequent larval stage, the protoscolex, depends on re-establishment of anterior identities within the metacestode germinative layer. It is, however, unclear so far how protoscolex differentiation in Echinococcus is regulated. We herein characterized the full complement of E. multilocularis TGFb/BMP receptors, which is composed of one type II and three type I receptor serine/threonine kinases. Functional analyzes showed that all Echinococcus TGFb/BMP receptors are enzymatically active and respond to host derived TGFb/BMP ligands for activating downstream Smad transcription factors. In situ hybridization experiments demonstrated that the Echinococcus TGFb/BMP receptors are mainly expressed by nerve and muscle cells within the germinative layer and in developing brood capsules. Interestingly, the production of brood capsules, which later give rise to protoscoleces, was strongly suppressed in the presence of inhibitors directed against TGFb/BMP receptors, whereas protoscolex differentiation was accelerated in response to host BMP2 and TGFb. Apart from being responsive to host TGFb/BMP ligands, protoscolex production also correlated with the expression of a parasite-derived TGFb-like ligand, EmACT, which is expressed in early brood capsules and which is strongly expressed in anterior domains during protoscolex development. Taken together, these data indicate an important role of TGFb/BMP signalling in Echinococcus anterior pole formation and protoscolex development. Since TGFb is accumulating around metacestode lesions at later stages of the infection, the host immune response could thus serve as a signal by which the parasite senses the time point at which protoscoleces must be produced. Overall, our data shed new light on molecular mechanisms of host-parasite interaction during AE and are relevant for the development of novel treatment strategies. |
dc.format.extent.es.fl_str_mv | 20 h. |
dc.format.mimetype.es.fl_str_mv | application/pdf |
dc.identifier.citation.es.fl_str_mv | Kaethner, M, Epping, K, Bernthaler, P [y otros autores]. "Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode". Frontiers in Cellular and Infection Microbiology. [en línea] 2023, 13: 1153117. 20 h. DOI: 10.3389/fcimb.2023.1153117. |
dc.identifier.doi.none.fl_str_mv | 10.3389/fcimb.2023.1153117 |
dc.identifier.issn.none.fl_str_mv | 2235-2988 |
dc.identifier.uri.none.fl_str_mv | https://hdl.handle.net/20.500.12008/43232 |
dc.language.iso.none.fl_str_mv | en eng |
dc.publisher.es.fl_str_mv | Frontiers |
dc.relation.ispartof.es.fl_str_mv | Frontiers in Cellular and Infection Microbiology, 2023, 13: 1153117. |
dc.rights.license.none.fl_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess |
dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
dc.subject.es.fl_str_mv | Echinococcosis TGFb BMP Protoscolex Brood capsulet Differentiation Body axes Development |
dc.title.none.fl_str_mv | Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode |
dc.type.es.fl_str_mv | Artículo |
dc.type.none.fl_str_mv | info:eu-repo/semantics/article |
dc.type.version.none.fl_str_mv | info:eu-repo/semantics/publishedVersion |
description | The lethal zoonosis alveolar echinococcosis (AE) is caused by tumor-like, infiltrative growth of the metacestode larval stage of the tapeworm Echinococcus multilocularis. We previously showed that the metacestode is composed of posteriorized tissue and that the production of the subsequent larval stage, the protoscolex, depends on re-establishment of anterior identities within the metacestode germinative layer. It is, however, unclear so far how protoscolex differentiation in Echinococcus is regulated. We herein characterized the full complement of E. multilocularis TGFb/BMP receptors, which is composed of one type II and three type I receptor serine/threonine kinases. Functional analyzes showed that all Echinococcus TGFb/BMP receptors are enzymatically active and respond to host derived TGFb/BMP ligands for activating downstream Smad transcription factors. In situ hybridization experiments demonstrated that the Echinococcus TGFb/BMP receptors are mainly expressed by nerve and muscle cells within the germinative layer and in developing brood capsules. Interestingly, the production of brood capsules, which later give rise to protoscoleces, was strongly suppressed in the presence of inhibitors directed against TGFb/BMP receptors, whereas protoscolex differentiation was accelerated in response to host BMP2 and TGFb. Apart from being responsive to host TGFb/BMP ligands, protoscolex production also correlated with the expression of a parasite-derived TGFb-like ligand, EmACT, which is expressed in early brood capsules and which is strongly expressed in anterior domains during protoscolex development. Taken together, these data indicate an important role of TGFb/BMP signalling in Echinococcus anterior pole formation and protoscolex development. Since TGFb is accumulating around metacestode lesions at later stages of the infection, the host immune response could thus serve as a signal by which the parasite senses the time point at which protoscoleces must be produced. Overall, our data shed new light on molecular mechanisms of host-parasite interaction during AE and are relevant for the development of novel treatment strategies. |
eu_rights_str_mv | openAccess |
format | article |
id | COLIBRI_1dfc3a83c5b2b8ce02c1d8787446b403 |
identifier_str_mv | Kaethner, M, Epping, K, Bernthaler, P [y otros autores]. "Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode". Frontiers in Cellular and Infection Microbiology. [en línea] 2023, 13: 1153117. 20 h. DOI: 10.3389/fcimb.2023.1153117. 2235-2988 10.3389/fcimb.2023.1153117 |
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 | COLIBRI |
network_name_str | COLIBRI |
oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/43232 |
publishDate | 2023 |
reponame_str | COLIBRI |
repository.mail.fl_str_mv | mabel.seroubian@seciu.edu.uy |
repository.name.fl_str_mv | COLIBRI - Universidad de la República |
repository_id_str | 4771 |
rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
spelling | Kaethner MarcEpping KerstinBernthaler PeterRudolf KilianThomann IrenaLeitschuh NadineBergmann MonikaSpiliotis MarkusKoziol Uriel, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.Brehm Klaus2024-03-20T13:54:27Z2024-03-20T13:54:27Z2023Kaethner, M, Epping, K, Bernthaler, P [y otros autores]. "Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode". Frontiers in Cellular and Infection Microbiology. [en línea] 2023, 13: 1153117. 20 h. DOI: 10.3389/fcimb.2023.1153117.2235-2988https://hdl.handle.net/20.500.12008/4323210.3389/fcimb.2023.1153117The lethal zoonosis alveolar echinococcosis (AE) is caused by tumor-like, infiltrative growth of the metacestode larval stage of the tapeworm Echinococcus multilocularis. We previously showed that the metacestode is composed of posteriorized tissue and that the production of the subsequent larval stage, the protoscolex, depends on re-establishment of anterior identities within the metacestode germinative layer. It is, however, unclear so far how protoscolex differentiation in Echinococcus is regulated. We herein characterized the full complement of E. multilocularis TGFb/BMP receptors, which is composed of one type II and three type I receptor serine/threonine kinases. Functional analyzes showed that all Echinococcus TGFb/BMP receptors are enzymatically active and respond to host derived TGFb/BMP ligands for activating downstream Smad transcription factors. In situ hybridization experiments demonstrated that the Echinococcus TGFb/BMP receptors are mainly expressed by nerve and muscle cells within the germinative layer and in developing brood capsules. Interestingly, the production of brood capsules, which later give rise to protoscoleces, was strongly suppressed in the presence of inhibitors directed against TGFb/BMP receptors, whereas protoscolex differentiation was accelerated in response to host BMP2 and TGFb. Apart from being responsive to host TGFb/BMP ligands, protoscolex production also correlated with the expression of a parasite-derived TGFb-like ligand, EmACT, which is expressed in early brood capsules and which is strongly expressed in anterior domains during protoscolex development. Taken together, these data indicate an important role of TGFb/BMP signalling in Echinococcus anterior pole formation and protoscolex development. Since TGFb is accumulating around metacestode lesions at later stages of the infection, the host immune response could thus serve as a signal by which the parasite senses the time point at which protoscoleces must be produced. Overall, our data shed new light on molecular mechanisms of host-parasite interaction during AE and are relevant for the development of novel treatment strategies.Submitted by Pintos Natalia (nataliapintosmvd@gmail.com) on 2024-03-19T16:00:51Z No. of bitstreams: 2 license_rdf: 24251 bytes, checksum: 71ed42ef0a0b648670f707320be37b90 (MD5) 10.3389.fcimb.2023.1153117.pdf: 10634723 bytes, checksum: bba7381a523f82b5c69f2fa86ae6de66 (MD5)Approved for entry into archive by Faget Cecilia (lfaget@fcien.edu.uy) on 2024-03-20T12:18:21Z (GMT) No. of bitstreams: 2 license_rdf: 24251 bytes, checksum: 71ed42ef0a0b648670f707320be37b90 (MD5) 10.3389.fcimb.2023.1153117.pdf: 10634723 bytes, checksum: bba7381a523f82b5c69f2fa86ae6de66 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2024-03-20T13:54:27Z (GMT). No. of bitstreams: 2 license_rdf: 24251 bytes, checksum: 71ed42ef0a0b648670f707320be37b90 (MD5) 10.3389.fcimb.2023.1153117.pdf: 10634723 bytes, checksum: bba7381a523f82b5c69f2fa86ae6de66 (MD5) Previous issue date: 202320 h.application/pdfenengFrontiersFrontiers in Cellular and Infection Microbiology, 2023, 13: 1153117.Las 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)EchinococcosisTGFbBMPProtoscolexBrood capsuletDifferentiationBody axesDevelopmentTransforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestodeArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaKaethner, MarcEpping, KerstinBernthaler, PeterRudolf, KilianThomann, IrenaLeitschuh, NadineBergmann, MonikaSpiliotis, MarkusKoziol, UrielBrehm, KlausLICENSElicense.txtlicense.txttext/plain; charset=utf-84267http://localhost:8080/xmlui/bitstream/20.500.12008/43232/5/license.txt6429389a7df7277b72b7924fdc7d47a9MD55CC-LICENSElicense_urllicense_urltext/plain; charset=utf-844http://localhost:8080/xmlui/bitstream/20.500.12008/43232/2/license_urla0ebbeafb9d2ec7cbb19d7137ebc392cMD52license_textlicense_texttext/html; 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- Universidad de la Repúblicafalse |
spellingShingle | Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode Kaethner, Marc Echinococcosis TGFb BMP Protoscolex Brood capsulet Differentiation Body axes Development |
status_str | publishedVersion |
title | Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode |
title_full | Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode |
title_fullStr | Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode |
title_full_unstemmed | Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode |
title_short | Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode |
title_sort | Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode |
topic | Echinococcosis TGFb BMP Protoscolex Brood capsulet Differentiation Body axes Development |
url | https://hdl.handle.net/20.500.12008/43232 |