Transforming growth factor-b signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode

Kaethner, Marc - Epping, Kerstin - Bernthaler, Peter - Rudolf, Kilian - Thomann, Irena - Leitschuh, Nadine - Bergmann, Monika - Spiliotis, Markus - Koziol, Uriel - Brehm, Klaus

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.


Detalles Bibliográficos
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.
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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
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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
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repository.mail.fl_str_mv mabel.seroubian@seciu.edu.uy
repository.name.fl_str_mv COLIBRI - Universidad de la República
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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