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
- Institución
- Instituto Nacional de Tecnología Agropecuaria
- OAI Identificador
- oai:localhost:20.500.12123/15303
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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)2025-09-29T13:46:07Zoai: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:l2025-09-29 13:46:07.894INTA 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 |
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INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria |
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tripaldi.nicolas@inta.gob.ar |
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