Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophages

Autores
Blanco, Federico Carlos; Vazquez, Cristina Lourdes; Bigi, María Mercedes; Rocha, Rosana Valeria; Garcia, Elizabeth Andrea; Bigi, Fabiana
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mycobacterium bovis, the causative agent of bovine tuberculosis, infects and persists within macrophages, triggering pro-inflammatory responses. While these mechanisms are well characterized for Mycobacterium tuberculosis, less is known about host responses to M. bovis. Inflammasome activation and IL-1β production have been linked to ESAT-6, a substrate of the ESX-1 secretion system present in both species. Here, we examined inflammasome activation in bovine macrophages infected with the virulent M. bovis strain Mb04-303. M. bovis AF2122/97 and NCTC10772 upregulated IL-1β transcription, whereas Mb04-303 and BCG did not. Unexpectedly, deletion of the genes encoding ESAT-6 and CFP-10 from Mb04-303 enhanced inflammasome activation, as evidenced by increased NLRP3 and IL-1β transcription. Complementation with either wild-type ESAT-6/CFP-10 or the T63A ESAT-6 variant restored downregulation of the response, indicating that this substitution does not alter inflammasome modulation. In contrast, deletion of ESAT-6/CFP-10 from an attenuated M. bovis vaccine candidate reduced IL-1β transcription. No differences were observed between M. tuberculosis H37Rv and its ESAT-6-deficient mutant in bovine macrophages. Together, these findings demonstrate that ESAT-6/CFP-10-mediated modulation of inflammasome activation in bovine macrophages is highly dependent on the mycobacterial genetic background.
Instituto de Biotecnología
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vazquez, Cristina Lourdes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Vazquez, Cristina Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Bigi, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rocha, Rosana Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Rocha, Rosana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garcia, Elizabeth Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Garcia, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
International Journal of Molecular Sciences 27 (9) : 4099 (May 2026)
Materia
Mycobacterium bovis
Macrófagos
Inflamación
Tuberculosis Bovina
Macrophages
Inflammation
Bovine Tuberculosis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/26164
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oai_identifier_str oai:localhost:20.500.12123/26164
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network_name_str INTA Digital (INTA)
spelling Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophagesBlanco, Federico CarlosVazquez, Cristina LourdesBigi, María MercedesRocha, Rosana ValeriaGarcia, Elizabeth AndreaBigi, FabianaMycobacterium bovisMacrófagosInflamaciónTuberculosis BovinaMacrophagesInflammationBovine TuberculosisMycobacterium bovis, the causative agent of bovine tuberculosis, infects and persists within macrophages, triggering pro-inflammatory responses. While these mechanisms are well characterized for Mycobacterium tuberculosis, less is known about host responses to M. bovis. Inflammasome activation and IL-1β production have been linked to ESAT-6, a substrate of the ESX-1 secretion system present in both species. Here, we examined inflammasome activation in bovine macrophages infected with the virulent M. bovis strain Mb04-303. M. bovis AF2122/97 and NCTC10772 upregulated IL-1β transcription, whereas Mb04-303 and BCG did not. Unexpectedly, deletion of the genes encoding ESAT-6 and CFP-10 from Mb04-303 enhanced inflammasome activation, as evidenced by increased NLRP3 and IL-1β transcription. Complementation with either wild-type ESAT-6/CFP-10 or the T63A ESAT-6 variant restored downregulation of the response, indicating that this substitution does not alter inflammasome modulation. In contrast, deletion of ESAT-6/CFP-10 from an attenuated M. bovis vaccine candidate reduced IL-1β transcription. No differences were observed between M. tuberculosis H37Rv and its ESAT-6-deficient mutant in bovine macrophages. Together, these findings demonstrate that ESAT-6/CFP-10-mediated modulation of inflammasome activation in bovine macrophages is highly dependent on the mycobacterial genetic background.Instituto de BiotecnologíaFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vazquez, Cristina Lourdes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Vazquez, Cristina Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Bigi, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rocha, Rosana Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Rocha, Rosana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Elizabeth Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Garcia, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMDPI2026-05-13T10:01:55Z2026-05-13T10:01:55Z2026-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/26164https://www.mdpi.com/1422-0067/27/9/40991422-0067https://doi.org/10.3390/ijms27094099International Journal of Molecular Sciences 27 (9) : 4099 (May 2026)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repograntAgreement/INTA/2023-PD-L06-I114, Desarrollo y aplicación de métodos diagnósticos y epidemiológicos para la producción pecuaria sustentable y agroalimentaria en humanos con foco en Una Saludinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2026-05-14T10:43:35Zoai:localhost:20.500.12123/26164instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2026-05-14 10:43:36.057INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophages
title Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophages
spellingShingle Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophages
Blanco, Federico Carlos
Mycobacterium bovis
Macrófagos
Inflamación
Tuberculosis Bovina
Macrophages
Inflammation
Bovine Tuberculosis
title_short Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophages
title_full Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophages
title_fullStr Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophages
title_full_unstemmed Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophages
title_sort Mycobacterium bovis strain-dependent effects of ESAT-6 and CFP-10 on inflammasome activation in bovine macrophages
dc.creator.none.fl_str_mv Blanco, Federico Carlos
Vazquez, Cristina Lourdes
Bigi, María Mercedes
Rocha, Rosana Valeria
Garcia, Elizabeth Andrea
Bigi, Fabiana
author Blanco, Federico Carlos
author_facet Blanco, Federico Carlos
Vazquez, Cristina Lourdes
Bigi, María Mercedes
Rocha, Rosana Valeria
Garcia, Elizabeth Andrea
Bigi, Fabiana
author_role author
author2 Vazquez, Cristina Lourdes
Bigi, María Mercedes
Rocha, Rosana Valeria
Garcia, Elizabeth Andrea
Bigi, Fabiana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Mycobacterium bovis
Macrófagos
Inflamación
Tuberculosis Bovina
Macrophages
Inflammation
Bovine Tuberculosis
topic Mycobacterium bovis
Macrófagos
Inflamación
Tuberculosis Bovina
Macrophages
Inflammation
Bovine Tuberculosis
dc.description.none.fl_txt_mv Mycobacterium bovis, the causative agent of bovine tuberculosis, infects and persists within macrophages, triggering pro-inflammatory responses. While these mechanisms are well characterized for Mycobacterium tuberculosis, less is known about host responses to M. bovis. Inflammasome activation and IL-1β production have been linked to ESAT-6, a substrate of the ESX-1 secretion system present in both species. Here, we examined inflammasome activation in bovine macrophages infected with the virulent M. bovis strain Mb04-303. M. bovis AF2122/97 and NCTC10772 upregulated IL-1β transcription, whereas Mb04-303 and BCG did not. Unexpectedly, deletion of the genes encoding ESAT-6 and CFP-10 from Mb04-303 enhanced inflammasome activation, as evidenced by increased NLRP3 and IL-1β transcription. Complementation with either wild-type ESAT-6/CFP-10 or the T63A ESAT-6 variant restored downregulation of the response, indicating that this substitution does not alter inflammasome modulation. In contrast, deletion of ESAT-6/CFP-10 from an attenuated M. bovis vaccine candidate reduced IL-1β transcription. No differences were observed between M. tuberculosis H37Rv and its ESAT-6-deficient mutant in bovine macrophages. Together, these findings demonstrate that ESAT-6/CFP-10-mediated modulation of inflammasome activation in bovine macrophages is highly dependent on the mycobacterial genetic background.
Instituto de Biotecnología
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vazquez, Cristina Lourdes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Vazquez, Cristina Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Bigi, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rocha, Rosana Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Rocha, Rosana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garcia, Elizabeth Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Garcia, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Mycobacterium bovis, the causative agent of bovine tuberculosis, infects and persists within macrophages, triggering pro-inflammatory responses. While these mechanisms are well characterized for Mycobacterium tuberculosis, less is known about host responses to M. bovis. Inflammasome activation and IL-1β production have been linked to ESAT-6, a substrate of the ESX-1 secretion system present in both species. Here, we examined inflammasome activation in bovine macrophages infected with the virulent M. bovis strain Mb04-303. M. bovis AF2122/97 and NCTC10772 upregulated IL-1β transcription, whereas Mb04-303 and BCG did not. Unexpectedly, deletion of the genes encoding ESAT-6 and CFP-10 from Mb04-303 enhanced inflammasome activation, as evidenced by increased NLRP3 and IL-1β transcription. Complementation with either wild-type ESAT-6/CFP-10 or the T63A ESAT-6 variant restored downregulation of the response, indicating that this substitution does not alter inflammasome modulation. In contrast, deletion of ESAT-6/CFP-10 from an attenuated M. bovis vaccine candidate reduced IL-1β transcription. No differences were observed between M. tuberculosis H37Rv and its ESAT-6-deficient mutant in bovine macrophages. Together, these findings demonstrate that ESAT-6/CFP-10-mediated modulation of inflammasome activation in bovine macrophages is highly dependent on the mycobacterial genetic background.
publishDate 2026
dc.date.none.fl_str_mv 2026-05-13T10:01:55Z
2026-05-13T10:01:55Z
2026-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/26164
https://www.mdpi.com/1422-0067/27/9/4099
1422-0067
https://doi.org/10.3390/ijms27094099
url http://hdl.handle.net/20.500.12123/26164
https://www.mdpi.com/1422-0067/27/9/4099
https://doi.org/10.3390/ijms27094099
identifier_str_mv 1422-0067
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repograntAgreement/INTA/2023-PD-L06-I114, Desarrollo y aplicación de métodos diagnósticos y epidemiológicos para la producción pecuaria sustentable y agroalimentaria en humanos con foco en Una Salud
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv International Journal of Molecular Sciences 27 (9) : 4099 (May 2026)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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