NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response

Introduction Neospora caninum is an apicomplexan parasite responsible for bovine neosporosis, a major cause of abortion in cattle worldwide. N. caninum rhoptry protein 2 (NcROP2) has been identified as an essential factor in host cell invasion and parasitophorous vacuole formation, making it a poten...

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Autores: Amieva, Rafael, Coronado, Montserrat, Powell, Jessica, Arranz Solís, David, Hassan, Musa A., Collantes Fernández, Esther, Ortega Mora, Luis Miguel, Horcajo Iglesias, María Del Pilar
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/124760
Acceso en línea:https://hdl.handle.net/20.500.14352/124760
Access Level:acceso abierto
Palabra clave:576.8
BALB/c
CRISPR/Cas9
NcROP2
Neospora caninum
Bovine macrophages
Transcriptome
Virulence factor
Parasitología (Veterinaria)
2401.12 Parasitología Animal
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oai_identifier_str oai:docta.ucm.es:20.500.14352/124760
network_acronym_str ES
network_name_str España
repository_id_str
spelling NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune responseAmieva, RafaelCoronado, MontserratPowell, JessicaArranz Solís, DavidHassan, Musa A.Collantes Fernández, EstherOrtega Mora, Luis MiguelHorcajo Iglesias, María Del Pilar576.8BALB/cCRISPR/Cas9NcROP2Neospora caninumBovine macrophagesTranscriptomeVirulence factorParasitología (Veterinaria)2401.12 Parasitología AnimalIntroduction Neospora caninum is an apicomplexan parasite responsible for bovine neosporosis, a major cause of abortion in cattle worldwide. N. caninum rhoptry protein 2 (NcROP2) has been identified as an essential factor in host cell invasion and parasitophorous vacuole formation, making it a potential target for disease control strategies. Methods In this study, we generated NcRop2 knockout (NcΔROP2) mutants using CRISPR/Cas9 technology to assess their role in parasite virulence. Results In a pregnant mouse model, NcΔROP2 parasites exhibited reduced virulence, as indicated by increased neonatal survival rates and lower parasite burden in the brain and attenuated clinical signs in the dams compared to the wild-type (Nc-Spain7) parental strain. Additionally, the NcΔROP2 mutants exhibited impaired proliferation and significantly induced the expression of interferon-stimulated genes in bovine monocyte-derived macrophages infected in vitro for 60 hours. Transcriptomic analysis further revealed a shift in parasite gene expression, with an upregulation of stress-related and bradyzoite markers. Functional assays confirmed that NcΔROP2 parasites were less susceptible to IFN-γ-mediated inhibition and displayed an enhanced ability to convert to the semi-dormant bradyzoite stage. Discussion These findings highlight NcROP2 as a key virulence factor involved in immune evasion and parasite proliferation, providing new insights into N. caninum infection pathogenesis and potential avenues for vaccine development.Frontiers MediaUniversidad Complutense de Madrid20252025-01-0120252025-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/124760reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1247602026-06-02T12:44:21Z
dc.title.none.fl_str_mv NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response
title NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response
spellingShingle NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response
Amieva, Rafael
576.8
BALB/c
CRISPR/Cas9
NcROP2
Neospora caninum
Bovine macrophages
Transcriptome
Virulence factor
Parasitología (Veterinaria)
2401.12 Parasitología Animal
title_short NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response
title_full NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response
title_fullStr NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response
title_full_unstemmed NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response
title_sort NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response
dc.creator.none.fl_str_mv Amieva, Rafael
Coronado, Montserrat
Powell, Jessica
Arranz Solís, David
Hassan, Musa A.
Collantes Fernández, Esther
Ortega Mora, Luis Miguel
Horcajo Iglesias, María Del Pilar
author Amieva, Rafael
author_facet Amieva, Rafael
Coronado, Montserrat
Powell, Jessica
Arranz Solís, David
Hassan, Musa A.
Collantes Fernández, Esther
Ortega Mora, Luis Miguel
Horcajo Iglesias, María Del Pilar
author_role author
author2 Coronado, Montserrat
Powell, Jessica
Arranz Solís, David
Hassan, Musa A.
Collantes Fernández, Esther
Ortega Mora, Luis Miguel
Horcajo Iglesias, María Del Pilar
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 576.8
BALB/c
CRISPR/Cas9
NcROP2
Neospora caninum
Bovine macrophages
Transcriptome
Virulence factor
Parasitología (Veterinaria)
2401.12 Parasitología Animal
topic 576.8
BALB/c
CRISPR/Cas9
NcROP2
Neospora caninum
Bovine macrophages
Transcriptome
Virulence factor
Parasitología (Veterinaria)
2401.12 Parasitología Animal
description Introduction Neospora caninum is an apicomplexan parasite responsible for bovine neosporosis, a major cause of abortion in cattle worldwide. N. caninum rhoptry protein 2 (NcROP2) has been identified as an essential factor in host cell invasion and parasitophorous vacuole formation, making it a potential target for disease control strategies. Methods In this study, we generated NcRop2 knockout (NcΔROP2) mutants using CRISPR/Cas9 technology to assess their role in parasite virulence. Results In a pregnant mouse model, NcΔROP2 parasites exhibited reduced virulence, as indicated by increased neonatal survival rates and lower parasite burden in the brain and attenuated clinical signs in the dams compared to the wild-type (Nc-Spain7) parental strain. Additionally, the NcΔROP2 mutants exhibited impaired proliferation and significantly induced the expression of interferon-stimulated genes in bovine monocyte-derived macrophages infected in vitro for 60 hours. Transcriptomic analysis further revealed a shift in parasite gene expression, with an upregulation of stress-related and bradyzoite markers. Functional assays confirmed that NcΔROP2 parasites were less susceptible to IFN-γ-mediated inhibition and displayed an enhanced ability to convert to the semi-dormant bradyzoite stage. Discussion These findings highlight NcROP2 as a key virulence factor involved in immune evasion and parasite proliferation, providing new insights into N. caninum infection pathogenesis and potential avenues for vaccine development.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/124760
url https://hdl.handle.net/20.500.14352/124760
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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