A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovis

Autores
Blanco, Federico Carlos; Bigi, María Mercedes; Garcia, Elizabeth Andrea; Elola, María Teresa; Vazquez, Cristina Lourdes; Bigi, Fabiana
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bovine tuberculosis is a chronic infectious disease primarily caused by Mycobacterium bovis, a bacterium that affects cattle and other mammals, including humans. Despite the availability of vast research about the immune response mechanisms of human tuberculosis caused by Mycobacterium tuberculosis, the knowledge of bovine tuberculosis’s immunology, particularly regarding the innate immune response, still remains scarce. In this study, we compared the transcriptome of cell cultures containing lymphocytes and M. bovis infected-macrophages with two strains of variable virulence, the virulent Mb04-303 strain and the attenuated Mb534. To that end, we infected bovine macrophages at a multiplicity of infection of one, and co-cultured the infections with autologous lymphocytes. RNA obtained from the co-cultures was sequenced to identify differentially expressed gene pathways by using the database Reactome. The RNA-seq analysis showed that the Mb04-303 infection upregulated the type 1 interferon signalling pathway, while it downregulated the KEAP1-NFE2L2 pathway. According to the literature, this last pathway is involved in the activation of antioxidant genes and inflammasome. In addition, the macrophages infected with Mb04-303 recruited more Galectin 8 than those infected with Mb534. This result indicates that Mb04-303 induced higher phagosome membrane damage, with the possible concomitant release of bacterial compounds into the cytoplasm that activates the type I signalling pathway. Altogether, Mb04-303 repressed the antioxidant and anti-inflammatory responses, likely impairing interleukin-1β activation, and trigged the canonical type 1 interferon signalling. Although these responses led to the control of bacterial replication during early infection, the virulent strain eventually managed to establish a successful infection.
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: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Biomédicas; Argentina
Fil: Bigi, María Mercedes. 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: Elola, María Teresa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro Paladini; 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, 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
Pathogens 12 (9) : 1159 (Septiembre 2023)
Materia
Bovine Tuberculosis
Interferons
Macrophages
Cattle
Natural Immunity
Immune Response
In vitro
Tuberculosis Bovina
Mycobacterium bovis
Interferonas
Macrofagos
Ganado Bovino
Inmunidad Natural
Respuesta Inmunológica
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:20.500.12123/15303
Acceder
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oai_identifier_str oai:localhost:20.500.12123/15303
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovisBlanco, Federico CarlosBigi, María MercedesGarcia, Elizabeth AndreaElola, María TeresaVazquez, Cristina LourdesBigi, FabianaBovine TuberculosisInterferonsMacrophagesCattleNatural ImmunityImmune ResponseIn vitroTuberculosis BovinaMycobacterium bovisInterferonasMacrofagosGanado BovinoInmunidad NaturalRespuesta InmunológicaBovine tuberculosis is a chronic infectious disease primarily caused by Mycobacterium bovis, a bacterium that affects cattle and other mammals, including humans. Despite the availability of vast research about the immune response mechanisms of human tuberculosis caused by Mycobacterium tuberculosis, the knowledge of bovine tuberculosis’s immunology, particularly regarding the innate immune response, still remains scarce. In this study, we compared the transcriptome of cell cultures containing lymphocytes and M. bovis infected-macrophages with two strains of variable virulence, the virulent Mb04-303 strain and the attenuated Mb534. To that end, we infected bovine macrophages at a multiplicity of infection of one, and co-cultured the infections with autologous lymphocytes. RNA obtained from the co-cultures was sequenced to identify differentially expressed gene pathways by using the database Reactome. The RNA-seq analysis showed that the Mb04-303 infection upregulated the type 1 interferon signalling pathway, while it downregulated the KEAP1-NFE2L2 pathway. According to the literature, this last pathway is involved in the activation of antioxidant genes and inflammasome. In addition, the macrophages infected with Mb04-303 recruited more Galectin 8 than those infected with Mb534. This result indicates that Mb04-303 induced higher phagosome membrane damage, with the possible concomitant release of bacterial compounds into the cytoplasm that activates the type I signalling pathway. Altogether, Mb04-303 repressed the antioxidant and anti-inflammatory responses, likely impairing interleukin-1β activation, and trigged the canonical type 1 interferon signalling. Although these responses led to the control of bacterial replication during early infection, the virulent strain eventually managed to establish a successful infection.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: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Biomédicas; ArgentinaFil: Bigi, María Mercedes. 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: Elola, María Teresa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro Paladini; 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, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMDPI2023-09-25T14:55:28Z2023-09-25T14:55:28Z2023-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/15303https://www.mdpi.com/2076-0817/12/9/11592076-0817https://doi.org/10.3390/pathogens12091159Pathogens 12 (9) : 1159 (Septiembre 2023)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repograntAgreement/INTA/2019-PD-E6-I116-001, Identificación y análisis funcional de genes o redes génicas de interés biotecnológico con fin agropecuario, forestal, agroalimentario y/o agroindustrial.info: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)2025-10-23T11:18:29Zoai:localhost:20.500.12123/15303instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-10-23 11:18:29.8INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovis
title A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovis
spellingShingle A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovis
Blanco, Federico Carlos
Bovine Tuberculosis
Interferons
Macrophages
Cattle
Natural Immunity
Immune Response
In vitro
Tuberculosis Bovina
Mycobacterium bovis
Interferonas
Macrofagos
Ganado Bovino
Inmunidad Natural
Respuesta Inmunológica
title_short A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovis
title_full A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovis
title_fullStr A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovis
title_full_unstemmed A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovis
title_sort A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the In vitro innate immune response against Mycobacterium bovis
dc.creator.none.fl_str_mv Blanco, Federico Carlos
Bigi, María Mercedes
Garcia, Elizabeth Andrea
Elola, María Teresa
Vazquez, Cristina Lourdes
Bigi, Fabiana
author Blanco, Federico Carlos
author_facet Blanco, Federico Carlos
Bigi, María Mercedes
Garcia, Elizabeth Andrea
Elola, María Teresa
Vazquez, Cristina Lourdes
Bigi, Fabiana
author_role author
author2 Bigi, María Mercedes
Garcia, Elizabeth Andrea
Elola, María Teresa
Vazquez, Cristina Lourdes
Bigi, Fabiana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Bovine Tuberculosis
Interferons
Macrophages
Cattle
Natural Immunity
Immune Response
In vitro
Tuberculosis Bovina
Mycobacterium bovis
Interferonas
Macrofagos
Ganado Bovino
Inmunidad Natural
Respuesta Inmunológica
topic Bovine Tuberculosis
Interferons
Macrophages
Cattle
Natural Immunity
Immune Response
In vitro
Tuberculosis Bovina
Mycobacterium bovis
Interferonas
Macrofagos
Ganado Bovino
Inmunidad Natural
Respuesta Inmunológica
dc.description.none.fl_txt_mv Bovine tuberculosis is a chronic infectious disease primarily caused by Mycobacterium bovis, a bacterium that affects cattle and other mammals, including humans. Despite the availability of vast research about the immune response mechanisms of human tuberculosis caused by Mycobacterium tuberculosis, the knowledge of bovine tuberculosis’s immunology, particularly regarding the innate immune response, still remains scarce. In this study, we compared the transcriptome of cell cultures containing lymphocytes and M. bovis infected-macrophages with two strains of variable virulence, the virulent Mb04-303 strain and the attenuated Mb534. To that end, we infected bovine macrophages at a multiplicity of infection of one, and co-cultured the infections with autologous lymphocytes. RNA obtained from the co-cultures was sequenced to identify differentially expressed gene pathways by using the database Reactome. The RNA-seq analysis showed that the Mb04-303 infection upregulated the type 1 interferon signalling pathway, while it downregulated the KEAP1-NFE2L2 pathway. According to the literature, this last pathway is involved in the activation of antioxidant genes and inflammasome. In addition, the macrophages infected with Mb04-303 recruited more Galectin 8 than those infected with Mb534. This result indicates that Mb04-303 induced higher phagosome membrane damage, with the possible concomitant release of bacterial compounds into the cytoplasm that activates the type I signalling pathway. Altogether, Mb04-303 repressed the antioxidant and anti-inflammatory responses, likely impairing interleukin-1β activation, and trigged the canonical type 1 interferon signalling. Although these responses led to the control of bacterial replication during early infection, the virulent strain eventually managed to establish a successful infection.
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: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Biomédicas; Argentina
Fil: Bigi, María Mercedes. 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: Elola, María Teresa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro Paladini; 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, 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 Bovine tuberculosis is a chronic infectious disease primarily caused by Mycobacterium bovis, a bacterium that affects cattle and other mammals, including humans. Despite the availability of vast research about the immune response mechanisms of human tuberculosis caused by Mycobacterium tuberculosis, the knowledge of bovine tuberculosis’s immunology, particularly regarding the innate immune response, still remains scarce. In this study, we compared the transcriptome of cell cultures containing lymphocytes and M. bovis infected-macrophages with two strains of variable virulence, the virulent Mb04-303 strain and the attenuated Mb534. To that end, we infected bovine macrophages at a multiplicity of infection of one, and co-cultured the infections with autologous lymphocytes. RNA obtained from the co-cultures was sequenced to identify differentially expressed gene pathways by using the database Reactome. The RNA-seq analysis showed that the Mb04-303 infection upregulated the type 1 interferon signalling pathway, while it downregulated the KEAP1-NFE2L2 pathway. According to the literature, this last pathway is involved in the activation of antioxidant genes and inflammasome. In addition, the macrophages infected with Mb04-303 recruited more Galectin 8 than those infected with Mb534. This result indicates that Mb04-303 induced higher phagosome membrane damage, with the possible concomitant release of bacterial compounds into the cytoplasm that activates the type I signalling pathway. Altogether, Mb04-303 repressed the antioxidant and anti-inflammatory responses, likely impairing interleukin-1β activation, and trigged the canonical type 1 interferon signalling. Although these responses led to the control of bacterial replication during early infection, the virulent strain eventually managed to establish a successful infection.
publishDate 2023
dc.date.none.fl_str_mv 2023-09-25T14:55:28Z
2023-09-25T14:55:28Z
2023-09
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/20.500.12123/15303
https://www.mdpi.com/2076-0817/12/9/1159
2076-0817
https://doi.org/10.3390/pathogens12091159
url http://hdl.handle.net/20.500.12123/15303
https://www.mdpi.com/2076-0817/12/9/1159
https://doi.org/10.3390/pathogens12091159
identifier_str_mv 2076-0817
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repograntAgreement/INTA/2019-PD-E6-I116-001, Identificación y análisis funcional de genes o redes génicas de interés biotecnológico con fin agropecuario, forestal, agroalimentario y/o agroindustrial.
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 Pathogens 12 (9) : 1159 (Septiembre 2023)
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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