Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTB
[EN] Paratuberculosis (PTB) is a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (Map). Genome-wide association studies revealed a significant enrichment of the keratinization pathway in cattle with multifocal lesions, suggesting a potential role of cytokeratins (CKs) in PTB...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de León |
| Repositorio: | BULERIA. Repositorio Institucional de la Universidad de León |
| OAI Identifier: | oai:dnet:buleria_____::9a9c9087ad778f15256d2b09b5dcc092 |
| Acceso en línea: | https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1690841/full https://hdl.handle.net/10612/28008 |
| Access Level: | acceso abierto |
| Palabra clave: | Sanidad animal Veterinaria Paratuberculosis Cytokeratin Epithelioid macrophages Granuloma Resilience 3109 Ciencias Veterinarias |
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Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTBNavarro León, Alejandra IsabelMuñoz, MartaBlanco Vázquez, CristinaIglesias, NataliaIglesias Cabo, TaniaCanive, MaríaBadia Bringué, GerardAlonso Hearn, MartaBalseiro Morales, Ana MaríaCasais, RosaSanidad animalVeterinariaParatuberculosisCytokeratinEpithelioid macrophagesGranulomaResilience3109 Ciencias Veterinarias[EN] Paratuberculosis (PTB) is a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (Map). Genome-wide association studies revealed a significant enrichment of the keratinization pathway in cattle with multifocal lesions, suggesting a potential role of cytokeratins (CKs) in PTB resilience mechanisms. To confirm this, the amount of CK-expressing cells was analyzed in granulomas from the distal jejunum (DJE) and jejunal lymph nodes (DJELN) of animals with focal, multifocal, and diffuse lesions, and in control animals without lesions. Quantitative double-immunohistochemical (D-IHC) analysis [using Iba1 (ionized calcium-binding adapter molecule-1) and CK, as specific markers of macrophages and epithelial cells, respectively] showed that animals with multifocal lesions had the highest numbers of double-Iba1/CK positive cells [epithelioid macrophages (EMs)]. Significant differences were observed with the focal (p < 0.001), diffuse (p = 0.038), and control groups (p < 0.001) in JELN. Similarly, these animals showed higher numbers of single-CK expressing cells in JELN and DJE. Two EM distribution patterns were observed. In Pattern 1, mostly observed in animals with multifocal lesions (low Map load, no clinical signs), EMs form a barrier-like arrangement around the granuloma, while in Pattern 2, mainly found in animals with diffuse lesions (high Map load, clinical signs), EMs have a diffuse arrangement throughout the granuloma. These findings suggest that animals with multifocal lesions might represent a resilient phenotype that controls Map infection and disease progression. This is achieved through the formation of ordered granulomas that prevent Map dissemination and maintain tissue integrity, which are characteristic features of resilient animals. CK could be considered a potential biomarker of PTB resilienceSIThe author(s) declare that financial support was received for the research and/or publication of this article. This study is part of the I+D+I project (PID2021-122195OR-C22), which was funded by the MCIN/AEI/10.13039/501100011033/ FEDER, UE, and by regional funding through SEKUENS Agency (PCTI 2024-2026. REF IDE/2024/000764) co-funded by FEDER. We acknowledge the National Institute for Agricultural Research (INIA) for the scholarships of Cristina Blanco Vázquez (CPD2016.0142) and Alejandra Isabel Navarro León (PRE20200- 096451), both funded by MCIN/AEI/10.13039/50110001033 and FSEFrontiers MediaSanidad AnimalFacultad de Veterinaria2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1690841/fullhttps://hdl.handle.net/10612/28008reponame:BULERIA. Repositorio Institucional de la Universidad de Leóninstname:Universidad de LeónIngléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:buleria_____::9a9c9087ad778f15256d2b09b5dcc0922026-06-24T12:43:27Z |
| dc.title.none.fl_str_mv |
Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTB |
| title |
Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTB |
| spellingShingle |
Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTB Navarro León, Alejandra Isabel Sanidad animal Veterinaria Paratuberculosis Cytokeratin Epithelioid macrophages Granuloma Resilience 3109 Ciencias Veterinarias |
| title_short |
Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTB |
| title_full |
Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTB |
| title_fullStr |
Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTB |
| title_full_unstemmed |
Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTB |
| title_sort |
Cytokeratin expression and distribution pattern of epithelioid macrophages in animals with different pathological forms of bovine paratuberculosis: potential role in resilience to PTB |
| dc.creator.none.fl_str_mv |
Navarro León, Alejandra Isabel Muñoz, Marta Blanco Vázquez, Cristina Iglesias, Natalia Iglesias Cabo, Tania Canive, María Badia Bringué, Gerard Alonso Hearn, Marta Balseiro Morales, Ana María Casais, Rosa |
| author |
Navarro León, Alejandra Isabel |
| author_facet |
Navarro León, Alejandra Isabel Muñoz, Marta Blanco Vázquez, Cristina Iglesias, Natalia Iglesias Cabo, Tania Canive, María Badia Bringué, Gerard Alonso Hearn, Marta Balseiro Morales, Ana María Casais, Rosa |
| author_role |
author |
| author2 |
Muñoz, Marta Blanco Vázquez, Cristina Iglesias, Natalia Iglesias Cabo, Tania Canive, María Badia Bringué, Gerard Alonso Hearn, Marta Balseiro Morales, Ana María Casais, Rosa |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Sanidad Animal Facultad de Veterinaria |
| dc.subject.none.fl_str_mv |
Sanidad animal Veterinaria Paratuberculosis Cytokeratin Epithelioid macrophages Granuloma Resilience 3109 Ciencias Veterinarias |
| topic |
Sanidad animal Veterinaria Paratuberculosis Cytokeratin Epithelioid macrophages Granuloma Resilience 3109 Ciencias Veterinarias |
| description |
[EN] Paratuberculosis (PTB) is a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (Map). Genome-wide association studies revealed a significant enrichment of the keratinization pathway in cattle with multifocal lesions, suggesting a potential role of cytokeratins (CKs) in PTB resilience mechanisms. To confirm this, the amount of CK-expressing cells was analyzed in granulomas from the distal jejunum (DJE) and jejunal lymph nodes (DJELN) of animals with focal, multifocal, and diffuse lesions, and in control animals without lesions. Quantitative double-immunohistochemical (D-IHC) analysis [using Iba1 (ionized calcium-binding adapter molecule-1) and CK, as specific markers of macrophages and epithelial cells, respectively] showed that animals with multifocal lesions had the highest numbers of double-Iba1/CK positive cells [epithelioid macrophages (EMs)]. Significant differences were observed with the focal (p < 0.001), diffuse (p = 0.038), and control groups (p < 0.001) in JELN. Similarly, these animals showed higher numbers of single-CK expressing cells in JELN and DJE. Two EM distribution patterns were observed. In Pattern 1, mostly observed in animals with multifocal lesions (low Map load, no clinical signs), EMs form a barrier-like arrangement around the granuloma, while in Pattern 2, mainly found in animals with diffuse lesions (high Map load, clinical signs), EMs have a diffuse arrangement throughout the granuloma. These findings suggest that animals with multifocal lesions might represent a resilient phenotype that controls Map infection and disease progression. This is achieved through the formation of ordered granulomas that prevent Map dissemination and maintain tissue integrity, which are characteristic features of resilient animals. CK could be considered a potential biomarker of PTB resilience |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1690841/full https://hdl.handle.net/10612/28008 |
| url |
https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1690841/full https://hdl.handle.net/10612/28008 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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Frontiers Media |
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Frontiers Media |
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reponame:BULERIA. Repositorio Institucional de la Universidad de León instname:Universidad de León |
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Universidad de León |
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BULERIA. Repositorio Institucional de la Universidad de León |
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BULERIA. Repositorio Institucional de la Universidad de León |
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