Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants

Autores
Rossi, Ursula Amaranta; Caffaro, María Eugenia; Gaute, Denice Noelia; Castaño Zubieta, Mirta Raquel; Maurizio, Estefanía; Poli, Mario Andres; Rossetti, Carlos Alberto
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Brucellosis in small ruminants is primarily caused by Brucella ovis and zoonotic B. melitensis. IRF3 is a key transcription factor for IFNα/β gene induction in response to intracellular pathogens. Previously, we identified a genetic association between the rs540 deletion (a-allele) in IRF3 exon 1 and an increased resistance to B. melitensis natural infection in goats. Here, we studied the effect of IRF3 exon 1 polymorphisms on monocyte-derived macrophages (MDMs) in vitro response to Brucella spp. infection, and on the humoral response of goats to Brucella vaccination. Caprine MDMs with the Aa-genotype for rs540 exhibited higher bacterial load (p < 0.01), decreased production of reactive oxygen species (p < 0.05) and lower induction of iNOS, IL-12b, IL-18 and IL-1α mRNA expression (p < 0.05) at 24 h post-infection (h p.i.) with B. melitensis 16 M, in comparison to the aa-genotype. Moreover, the A-allele was associated with an early negativization to Brucella Buffered Plate Antigen test (p < 0.05) and reduced IgG antibody responses (p < 0.05) after Brucella vaccination in goats. On the other hand, ovine MDMs with the T-T-allele for the haplotype rs853-rs301 in IRF3 exon 1 exhibited lower bacterial loads and intracellular bacteria survival rates (ISR) at 24 h p.i. with B. melitensis Rev. 1 and B. ovis PA (p < 0.05), and reduced production of reactive nitrogen species and anion superoxide at 48 h p.i. with B. ovis (p < 0.001). In summary, these results show that polymorphisms in IRF3 exon 1 can influence the immune response of small ruminants to Brucella infection.
Instituto de Patobiología
Fil: Rossi, Ursula Amaranta. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Rossi, Ursula Amaranta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Caffaro, Marí­a Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina
Fil: Gaute, Denice Noelia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Gaute, Denice Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castaño Zubieta, Mirta Raquel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Castaño Zubieta, Mirta Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Maurizio, Estefania. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Maurizio, Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina
Fil: Rossetti, Carlos Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Rossetti, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
Mammalian Genome 37 : 45 (March 2026)
Materia
Polymorphism
Immune Response
Brucella
Small Ruminants
Polimorfismo
Respuesta Inmunológica
Pequeños Rumiantes
Nivel de accesibilidad
acceso restringido
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:20.500.12123/25688
Acceder
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oai_identifier_str oai:localhost:20.500.12123/25688
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminantsRossi, Ursula AmarantaCaffaro, María EugeniaGaute, Denice NoeliaCastaño Zubieta, Mirta RaquelMaurizio, EstefaníaPoli, Mario AndresRossetti, Carlos AlbertoPolymorphismImmune ResponseBrucellaSmall RuminantsPolimorfismoRespuesta InmunológicaPequeños RumiantesBrucellosis in small ruminants is primarily caused by Brucella ovis and zoonotic B. melitensis. IRF3 is a key transcription factor for IFNα/β gene induction in response to intracellular pathogens. Previously, we identified a genetic association between the rs540 deletion (a-allele) in IRF3 exon 1 and an increased resistance to B. melitensis natural infection in goats. Here, we studied the effect of IRF3 exon 1 polymorphisms on monocyte-derived macrophages (MDMs) in vitro response to Brucella spp. infection, and on the humoral response of goats to Brucella vaccination. Caprine MDMs with the Aa-genotype for rs540 exhibited higher bacterial load (p < 0.01), decreased production of reactive oxygen species (p < 0.05) and lower induction of iNOS, IL-12b, IL-18 and IL-1α mRNA expression (p < 0.05) at 24 h post-infection (h p.i.) with B. melitensis 16 M, in comparison to the aa-genotype. Moreover, the A-allele was associated with an early negativization to Brucella Buffered Plate Antigen test (p < 0.05) and reduced IgG antibody responses (p < 0.05) after Brucella vaccination in goats. On the other hand, ovine MDMs with the T-T-allele for the haplotype rs853-rs301 in IRF3 exon 1 exhibited lower bacterial loads and intracellular bacteria survival rates (ISR) at 24 h p.i. with B. melitensis Rev. 1 and B. ovis PA (p < 0.05), and reduced production of reactive nitrogen species and anion superoxide at 48 h p.i. with B. ovis (p < 0.001). In summary, these results show that polymorphisms in IRF3 exon 1 can influence the immune response of small ruminants to Brucella infection.Instituto de PatobiologíaFil: Rossi, Ursula Amaranta. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; ArgentinaFil: Rossi, Ursula Amaranta. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caffaro, Marí­a Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Gaute, Denice Noelia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; ArgentinaFil: Gaute, Denice Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castaño Zubieta, Mirta Raquel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; ArgentinaFil: Castaño Zubieta, Mirta Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maurizio, Estefania. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; ArgentinaFil: Maurizio, Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Rossetti, Carlos Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; ArgentinaFil: Rossetti, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaSpringer2026-04-07T10:26:23Z2026-04-07T10:26:23Z2026-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/25688https://link.springer.com/article/10.1007/s00335-026-10212-91432-17770938-8990https://doi.org/10.1007/s00335-026-10212-9Mammalian Genome 37 : 45 (March 2026)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repograntAgreement/INTA/2023-PD-L01-I113, Herramientas de estudio de la Patogenia e Inmunidad en agentes infecciosos y tóxicos que aporten a la sustentabilidad de la producción pecuaria en el marco de Una Saludinfo:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2026-04-16T09:53:30Zoai:localhost:20.500.12123/25688instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2026-04-16 09:53:31.232INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants
title Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants
spellingShingle Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants
Rossi, Ursula Amaranta
Polymorphism
Immune Response
Brucella
Small Ruminants
Polimorfismo
Respuesta Inmunológica
Pequeños Rumiantes
title_short Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants
title_full Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants
title_fullStr Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants
title_full_unstemmed Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants
title_sort Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants
dc.creator.none.fl_str_mv Rossi, Ursula Amaranta
Caffaro, María Eugenia
Gaute, Denice Noelia
Castaño Zubieta, Mirta Raquel
Maurizio, Estefanía
Poli, Mario Andres
Rossetti, Carlos Alberto
author Rossi, Ursula Amaranta
author_facet Rossi, Ursula Amaranta
Caffaro, María Eugenia
Gaute, Denice Noelia
Castaño Zubieta, Mirta Raquel
Maurizio, Estefanía
Poli, Mario Andres
Rossetti, Carlos Alberto
author_role author
author2 Caffaro, María Eugenia
Gaute, Denice Noelia
Castaño Zubieta, Mirta Raquel
Maurizio, Estefanía
Poli, Mario Andres
Rossetti, Carlos Alberto
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Polymorphism
Immune Response
Brucella
Small Ruminants
Polimorfismo
Respuesta Inmunológica
Pequeños Rumiantes
topic Polymorphism
Immune Response
Brucella
Small Ruminants
Polimorfismo
Respuesta Inmunológica
Pequeños Rumiantes
dc.description.none.fl_txt_mv Brucellosis in small ruminants is primarily caused by Brucella ovis and zoonotic B. melitensis. IRF3 is a key transcription factor for IFNα/β gene induction in response to intracellular pathogens. Previously, we identified a genetic association between the rs540 deletion (a-allele) in IRF3 exon 1 and an increased resistance to B. melitensis natural infection in goats. Here, we studied the effect of IRF3 exon 1 polymorphisms on monocyte-derived macrophages (MDMs) in vitro response to Brucella spp. infection, and on the humoral response of goats to Brucella vaccination. Caprine MDMs with the Aa-genotype for rs540 exhibited higher bacterial load (p < 0.01), decreased production of reactive oxygen species (p < 0.05) and lower induction of iNOS, IL-12b, IL-18 and IL-1α mRNA expression (p < 0.05) at 24 h post-infection (h p.i.) with B. melitensis 16 M, in comparison to the aa-genotype. Moreover, the A-allele was associated with an early negativization to Brucella Buffered Plate Antigen test (p < 0.05) and reduced IgG antibody responses (p < 0.05) after Brucella vaccination in goats. On the other hand, ovine MDMs with the T-T-allele for the haplotype rs853-rs301 in IRF3 exon 1 exhibited lower bacterial loads and intracellular bacteria survival rates (ISR) at 24 h p.i. with B. melitensis Rev. 1 and B. ovis PA (p < 0.05), and reduced production of reactive nitrogen species and anion superoxide at 48 h p.i. with B. ovis (p < 0.001). In summary, these results show that polymorphisms in IRF3 exon 1 can influence the immune response of small ruminants to Brucella infection.
Instituto de Patobiología
Fil: Rossi, Ursula Amaranta. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Rossi, Ursula Amaranta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Caffaro, Marí­a Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina
Fil: Gaute, Denice Noelia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Gaute, Denice Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castaño Zubieta, Mirta Raquel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Castaño Zubieta, Mirta Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Maurizio, Estefania. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Maurizio, Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina
Fil: Rossetti, Carlos Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Rossetti, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Brucellosis in small ruminants is primarily caused by Brucella ovis and zoonotic B. melitensis. IRF3 is a key transcription factor for IFNα/β gene induction in response to intracellular pathogens. Previously, we identified a genetic association between the rs540 deletion (a-allele) in IRF3 exon 1 and an increased resistance to B. melitensis natural infection in goats. Here, we studied the effect of IRF3 exon 1 polymorphisms on monocyte-derived macrophages (MDMs) in vitro response to Brucella spp. infection, and on the humoral response of goats to Brucella vaccination. Caprine MDMs with the Aa-genotype for rs540 exhibited higher bacterial load (p < 0.01), decreased production of reactive oxygen species (p < 0.05) and lower induction of iNOS, IL-12b, IL-18 and IL-1α mRNA expression (p < 0.05) at 24 h post-infection (h p.i.) with B. melitensis 16 M, in comparison to the aa-genotype. Moreover, the A-allele was associated with an early negativization to Brucella Buffered Plate Antigen test (p < 0.05) and reduced IgG antibody responses (p < 0.05) after Brucella vaccination in goats. On the other hand, ovine MDMs with the T-T-allele for the haplotype rs853-rs301 in IRF3 exon 1 exhibited lower bacterial loads and intracellular bacteria survival rates (ISR) at 24 h p.i. with B. melitensis Rev. 1 and B. ovis PA (p < 0.05), and reduced production of reactive nitrogen species and anion superoxide at 48 h p.i. with B. ovis (p < 0.001). In summary, these results show that polymorphisms in IRF3 exon 1 can influence the immune response of small ruminants to Brucella infection.
publishDate 2026
dc.date.none.fl_str_mv 2026-04-07T10:26:23Z
2026-04-07T10:26:23Z
2026-03
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/20.500.12123/25688
https://link.springer.com/article/10.1007/s00335-026-10212-9
1432-1777
0938-8990
https://doi.org/10.1007/s00335-026-10212-9
url http://hdl.handle.net/20.500.12123/25688
https://link.springer.com/article/10.1007/s00335-026-10212-9
https://doi.org/10.1007/s00335-026-10212-9
identifier_str_mv 1432-1777
0938-8990
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repograntAgreement/INTA/2023-PD-L01-I113, Herramientas de estudio de la Patogenia e Inmunidad en agentes infecciosos y tóxicos que aporten a la sustentabilidad de la producción pecuaria en el marco de Una Salud
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
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 restrictedAccess
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 Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv Mammalian Genome 37 : 45 (March 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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