Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses

Macrophages (MØs) are pivotal immune cells exhibiting significant plasticity that hasbeenwidelystudiedinhumanandmurinemodels.Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are key regulators of macrophage differentiation from monocytes. In...

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Autores: Hecker, Yanina P, Coronado, Montserrat, Hurtado-Morillas, Clara, Arranz-Solís, David, Sánchez-Sánchez, Roberto, Corbí, Ángel, Ortega-Mora, Luis Miguel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/413137
Acceso en línea:http://hdl.handle.net/10261/413137
Access Level:acceso abierto
Palabra clave:GM-CSF immunophenotype
M-CSF
ovine macrophages
RNAseq
immunophenotype
id ES_99556ec25ac59b1753620dccff5b8326
oai_identifier_str oai:digital.csic.es:10261/413137
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses
title Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses
spellingShingle Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses
Hecker, Yanina P
GM-CSF immunophenotype
M-CSF
ovine macrophages
RNAseq
immunophenotype
M-CSF
ovine macrophages
RNAseq
title_short Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses
title_full Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses
title_fullStr Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses
title_full_unstemmed Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses
title_sort Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses
dc.creator.none.fl_str_mv Hecker, Yanina P
Coronado, Montserrat
Hurtado-Morillas, Clara
Arranz-Solís, David
Sánchez-Sánchez, Roberto
Corbí, Ángel
Ortega-Mora, Luis Miguel
author Hecker, Yanina P
author_facet Hecker, Yanina P
Coronado, Montserrat
Hurtado-Morillas, Clara
Arranz-Solís, David
Sánchez-Sánchez, Roberto
Corbí, Ángel
Ortega-Mora, Luis Miguel
author_role author
author2 Coronado, Montserrat
Hurtado-Morillas, Clara
Arranz-Solís, David
Sánchez-Sánchez, Roberto
Corbí, Ángel
Ortega-Mora, Luis Miguel
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Comunidad de Madrid
Ministerio de Ciencia e Innovación (España)
Hecker, Yanina P [0000-0001-9316-0588]
Coronado, Montserrat [0009-0004-5499-4132]
Hurtado-Morillas, Clara [0000-0001-8041-4980]
Arranz-Solís, David [0000-0002-2647-3194]
Sánchez-Sánchez, Roberto [0000-0002-5067-2636]
Corbí, Ángel [0000-0003-1980-5733]
Ortega-Mora, Luis Miguel [0000-0002-4986-6783]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv GM-CSF immunophenotype
M-CSF
ovine macrophages
RNAseq
immunophenotype

M-CSF
ovine macrophages
RNAseq
topic GM-CSF immunophenotype
M-CSF
ovine macrophages
RNAseq
immunophenotype
M-CSF
ovine macrophages
RNAseq
description Macrophages (MØs) are pivotal immune cells exhibiting significant plasticity that hasbeenwidelystudiedinhumanandmurinemodels.Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are key regulators of macrophage differentiation from monocytes. In this study, we comprehensively investigated the immunophenotypic, functional, andtranscriptomic profiles of ovine MØsdifferentiated with GM-CSF(GM-oMØs) or M-CSF(M-oMØs)toprovideamorenuancedunderstandingoftheiractivation states. After 7 days, GM-oMØs displayed a smaller, more varied morphology with lower cell yields compared to the larger, uniformly amoeboid M-oMØs. Immunophenotypically, M-oMØs showed significantly higher CD163 expression, consistent with human M-MØs, while CLEC5A was uninformative for differentiation. Transcriptomic analysis, complemented by qPCR and ELISA, revealed clearly distinct profiles, with GM-oMØs exhibiting a pronounced pro inflammatory phenotype and showing significantly higher expression of 408 genes, mostly associated with interferon and inflammatory response pathways, a feature that aligns with the functional and phenotypic characteristics of human and mouse GM-MØ. Conversely, M-oMØs displayed a regulatory and anti inflammatory profile, marked by a significantly higher expression of IL-10 and a set of 248 genes involved in cellular homeostasis. Notably, LPS stimulation dramatically shifted the M-oMØ phenotype toward a pro-inflammatory state, unequivocally demonstrating their substantial plasticity, and mirroring human M CSF-polarized monocytes. Our findings fundamentally challenge the prevailing M1/M2 simplification in ovine macrophage biology and provide a robust foundation for selecting appropriate in vitro macrophage models for future investigations into ovine host defense and disease pathogenesis. This study demonstrated that M-oMØs exhibit greater plasticity, making them more suitable for pathogen-host interaction studies. Unlike GM macrophages, which already have a defined phenotype, M-oMØs more accurately reflect the dynamic immune response induced by a pathogen in the host.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/413137
url http://hdl.handle.net/10261/413137
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
2023-T1/SAL-GL29230/ATRACCIÓN TALENTO CESAR NOMBELA 2023
TEC-2024/BIO-66/SALAINDEC-CM
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138673OB-C21
http.//dx.doi.org/10.3389/fimmu.2025.1680086
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
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spelling Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responsesHecker, Yanina PCoronado, MontserratHurtado-Morillas, ClaraArranz-Solís, DavidSánchez-Sánchez, RobertoCorbí, ÁngelOrtega-Mora, Luis MiguelGM-CSF immunophenotypeM-CSFovine macrophagesRNAseqimmunophenotypeM-CSFovine macrophagesRNAseqMacrophages (MØs) are pivotal immune cells exhibiting significant plasticity that hasbeenwidelystudiedinhumanandmurinemodels.Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are key regulators of macrophage differentiation from monocytes. In this study, we comprehensively investigated the immunophenotypic, functional, andtranscriptomic profiles of ovine MØsdifferentiated with GM-CSF(GM-oMØs) or M-CSF(M-oMØs)toprovideamorenuancedunderstandingoftheiractivation states. After 7 days, GM-oMØs displayed a smaller, more varied morphology with lower cell yields compared to the larger, uniformly amoeboid M-oMØs. Immunophenotypically, M-oMØs showed significantly higher CD163 expression, consistent with human M-MØs, while CLEC5A was uninformative for differentiation. Transcriptomic analysis, complemented by qPCR and ELISA, revealed clearly distinct profiles, with GM-oMØs exhibiting a pronounced pro inflammatory phenotype and showing significantly higher expression of 408 genes, mostly associated with interferon and inflammatory response pathways, a feature that aligns with the functional and phenotypic characteristics of human and mouse GM-MØ. Conversely, M-oMØs displayed a regulatory and anti inflammatory profile, marked by a significantly higher expression of IL-10 and a set of 248 genes involved in cellular homeostasis. Notably, LPS stimulation dramatically shifted the M-oMØ phenotype toward a pro-inflammatory state, unequivocally demonstrating their substantial plasticity, and mirroring human M CSF-polarized monocytes. Our findings fundamentally challenge the prevailing M1/M2 simplification in ovine macrophage biology and provide a robust foundation for selecting appropriate in vitro macrophage models for future investigations into ovine host defense and disease pathogenesis. This study demonstrated that M-oMØs exhibit greater plasticity, making them more suitable for pathogen-host interaction studies. Unlike GM macrophages, which already have a defined phenotype, M-oMØs more accurately reflect the dynamic immune response induced by a pathogen in the host.The author(s) declare financial support was received for the research and/or publication of this article. This research was supported by the projects funded by the Madrid Government (“Atracción de Talento César Nombela” [2023-T1/SAL-GL 29230]). Additional funds were received from the Spanish Ministry of Science and Innovation (PID2022-138673OB-C21) and the General Directorate of Research and Innovation of the Regional Government of Madrid (TEC-2024/BIO-66/ SALAINDEC-CM). YPH is funded by “Atracción de Talento César Nombela” (2023-T1/SAL-GL-29230)Peer reviewedFrontiers MediaComunidad de MadridMinisterio de Ciencia e Innovación (España)Hecker, Yanina P [0000-0001-9316-0588]Coronado, Montserrat [0009-0004-5499-4132]Hurtado-Morillas, Clara [0000-0001-8041-4980]Arranz-Solís, David [0000-0002-2647-3194]Sánchez-Sánchez, Roberto [0000-0002-5067-2636]Corbí, Ángel [0000-0003-1980-5733]Ortega-Mora, Luis Miguel [0000-0002-4986-6783]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/413137reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#2023-T1/SAL-GL29230/ATRACCIÓN TALENTO CESAR NOMBELA 2023TEC-2024/BIO-66/SALAINDEC-CMinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138673OB-C21http.//dx.doi.org/10.3389/fimmu.2025.1680086Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4131372026-05-22T06:33:51Z
score 15,81155

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