Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells

Autores
Serafino, Agustina; Bertinat, Yasmín Ayelén; Bueno, Jorgelina; Pittaluga, Jose; Birnberg Weiss, Federico; Milillo, María Ayelén; Barrionuevo, Paula
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Brucella abortus (Ba) is a pathogen that survives inside macrophages. Despite being itspreferential niche, Ba infects other cells, as shown by the multiple signs and symptomshumans present. This pathogen can evade our immune system. Ba displays a mechanismof down-modulating MHC-I on monocytes/macrophages in the presence of IFN-γ (whenTh1 response is triggered) without altering the total expression of MHC-I. The retainedMHC-I proteins are located within the Golgi Apparatus (GA). The RNA of Ba is one of thePAMPs that trigger this phenomenon. However, we acknowledged whether this event couldbe triggered in other cells relevant during Ba infection. Here, we demonstrate that Ba RNAreduced the surface expression of MHC-I induced by IFN-γ in the human bronchial epithelium(Calu-6), the human alveolar epithelium (A-549) and the endothelial microvasculature(HMEC) cell lines. In Calu-6 and HMEC cells, Ba RNA induces the retention of MHC-I in theGA. This phenomenon was not observed in A-549 cells. We then evaluated the effect of BaRNA on the secretion of IL-8, IL-6 and MCP-1, key cytokines in Ba infection. Contrary to ourexpectations, HMEC, Calu-6 and A-549 cells treated with Ba RNA had higher IL-8 and IL-6levels compared to untreated cells. In addition, we showed that Ba RNA down-modulatesthe MHC-I surface expression induced by IFN-γ on human monocytes/macrophages via thepathway of the Epidermal Growth Factor Receptor (EGFR). So, cells were stimulated withan EGFR ligand-blocking antibody (Cetuximab) and Ba RNA. Neutralization of the EGFR tosome extent reversed the down-modulation of MHC-I mediated by Ba RNA in HMEC and A-549 cells. In conclusion, this is the first study exploring a central immune evasion strategy,such as the downregulation of MHC-I surface expression, beyond monocytes and couldshed light on how it persists effectively within the host, enduring unseen and escaping CD8+T cell surveillance.
Fil: Serafino, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bertinat, Yasmín Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bueno, Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Pittaluga, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Birnberg Weiss, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Milillo, María Ayelén. Universidad Nacional de Río Negro. Sede Andina. Centro de Estudios en Ciencia, Tecnología, Cultura y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
BRUCELLA ABORTUS
RNA
ENDOTHELIAL CELLS
EPITHELIAL CELLS
IMMUNE EVASION STRATEGIES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/240939
Acceder
id CONICETDig_73f54abcf5447c051cf3386e1b076d97
oai_identifier_str oai:ri.conicet.gov.ar:11336/240939
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cellsSerafino, AgustinaBertinat, Yasmín AyelénBueno, JorgelinaPittaluga, JoseBirnberg Weiss, FedericoMilillo, María AyelénBarrionuevo, PaulaBRUCELLA ABORTUSRNAENDOTHELIAL CELLSEPITHELIAL CELLSIMMUNE EVASION STRATEGIEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Brucella abortus (Ba) is a pathogen that survives inside macrophages. Despite being itspreferential niche, Ba infects other cells, as shown by the multiple signs and symptomshumans present. This pathogen can evade our immune system. Ba displays a mechanismof down-modulating MHC-I on monocytes/macrophages in the presence of IFN-γ (whenTh1 response is triggered) without altering the total expression of MHC-I. The retainedMHC-I proteins are located within the Golgi Apparatus (GA). The RNA of Ba is one of thePAMPs that trigger this phenomenon. However, we acknowledged whether this event couldbe triggered in other cells relevant during Ba infection. Here, we demonstrate that Ba RNAreduced the surface expression of MHC-I induced by IFN-γ in the human bronchial epithelium(Calu-6), the human alveolar epithelium (A-549) and the endothelial microvasculature(HMEC) cell lines. In Calu-6 and HMEC cells, Ba RNA induces the retention of MHC-I in theGA. This phenomenon was not observed in A-549 cells. We then evaluated the effect of BaRNA on the secretion of IL-8, IL-6 and MCP-1, key cytokines in Ba infection. Contrary to ourexpectations, HMEC, Calu-6 and A-549 cells treated with Ba RNA had higher IL-8 and IL-6levels compared to untreated cells. In addition, we showed that Ba RNA down-modulatesthe MHC-I surface expression induced by IFN-γ on human monocytes/macrophages via thepathway of the Epidermal Growth Factor Receptor (EGFR). So, cells were stimulated withan EGFR ligand-blocking antibody (Cetuximab) and Ba RNA. Neutralization of the EGFR tosome extent reversed the down-modulation of MHC-I mediated by Ba RNA in HMEC and A-549 cells. In conclusion, this is the first study exploring a central immune evasion strategy,such as the downregulation of MHC-I surface expression, beyond monocytes and couldshed light on how it persists effectively within the host, enduring unseen and escaping CD8+T cell surveillance.Fil: Serafino, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bertinat, Yasmín Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bueno, Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pittaluga, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Birnberg Weiss, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Milillo, María Ayelén. Universidad Nacional de Río Negro. Sede Andina. Centro de Estudios en Ciencia, Tecnología, Cultura y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaPublic Library of Science2024-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/240939Serafino, Agustina; Bertinat, Yasmín Ayelén; Bueno, Jorgelina; Pittaluga, Jose; Birnberg Weiss, Federico; et al.; Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells; Public Library of Science; Plos One; 19; 7; 7-2024; 1-161932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.pone.0306429info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0306429info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:50:59Zoai:ri.conicet.gov.ar:11336/240939instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:50:59.434CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells
title Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells
spellingShingle Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells
Serafino, Agustina
BRUCELLA ABORTUS
RNA
ENDOTHELIAL CELLS
EPITHELIAL CELLS
IMMUNE EVASION STRATEGIES
title_short Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells
title_full Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells
title_fullStr Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells
title_full_unstemmed Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells
title_sort Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells
dc.creator.none.fl_str_mv Serafino, Agustina
Bertinat, Yasmín Ayelén
Bueno, Jorgelina
Pittaluga, Jose
Birnberg Weiss, Federico
Milillo, María Ayelén
Barrionuevo, Paula
author Serafino, Agustina
author_facet Serafino, Agustina
Bertinat, Yasmín Ayelén
Bueno, Jorgelina
Pittaluga, Jose
Birnberg Weiss, Federico
Milillo, María Ayelén
Barrionuevo, Paula
author_role author
author2 Bertinat, Yasmín Ayelén
Bueno, Jorgelina
Pittaluga, Jose
Birnberg Weiss, Federico
Milillo, María Ayelén
Barrionuevo, Paula
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv BRUCELLA ABORTUS
RNA
ENDOTHELIAL CELLS
EPITHELIAL CELLS
IMMUNE EVASION STRATEGIES
topic BRUCELLA ABORTUS
RNA
ENDOTHELIAL CELLS
EPITHELIAL CELLS
IMMUNE EVASION STRATEGIES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Brucella abortus (Ba) is a pathogen that survives inside macrophages. Despite being itspreferential niche, Ba infects other cells, as shown by the multiple signs and symptomshumans present. This pathogen can evade our immune system. Ba displays a mechanismof down-modulating MHC-I on monocytes/macrophages in the presence of IFN-γ (whenTh1 response is triggered) without altering the total expression of MHC-I. The retainedMHC-I proteins are located within the Golgi Apparatus (GA). The RNA of Ba is one of thePAMPs that trigger this phenomenon. However, we acknowledged whether this event couldbe triggered in other cells relevant during Ba infection. Here, we demonstrate that Ba RNAreduced the surface expression of MHC-I induced by IFN-γ in the human bronchial epithelium(Calu-6), the human alveolar epithelium (A-549) and the endothelial microvasculature(HMEC) cell lines. In Calu-6 and HMEC cells, Ba RNA induces the retention of MHC-I in theGA. This phenomenon was not observed in A-549 cells. We then evaluated the effect of BaRNA on the secretion of IL-8, IL-6 and MCP-1, key cytokines in Ba infection. Contrary to ourexpectations, HMEC, Calu-6 and A-549 cells treated with Ba RNA had higher IL-8 and IL-6levels compared to untreated cells. In addition, we showed that Ba RNA down-modulatesthe MHC-I surface expression induced by IFN-γ on human monocytes/macrophages via thepathway of the Epidermal Growth Factor Receptor (EGFR). So, cells were stimulated withan EGFR ligand-blocking antibody (Cetuximab) and Ba RNA. Neutralization of the EGFR tosome extent reversed the down-modulation of MHC-I mediated by Ba RNA in HMEC and A-549 cells. In conclusion, this is the first study exploring a central immune evasion strategy,such as the downregulation of MHC-I surface expression, beyond monocytes and couldshed light on how it persists effectively within the host, enduring unseen and escaping CD8+T cell surveillance.
Fil: Serafino, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bertinat, Yasmín Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bueno, Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Pittaluga, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Birnberg Weiss, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Milillo, María Ayelén. Universidad Nacional de Río Negro. Sede Andina. Centro de Estudios en Ciencia, Tecnología, Cultura y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Brucella abortus (Ba) is a pathogen that survives inside macrophages. Despite being itspreferential niche, Ba infects other cells, as shown by the multiple signs and symptomshumans present. This pathogen can evade our immune system. Ba displays a mechanismof down-modulating MHC-I on monocytes/macrophages in the presence of IFN-γ (whenTh1 response is triggered) without altering the total expression of MHC-I. The retainedMHC-I proteins are located within the Golgi Apparatus (GA). The RNA of Ba is one of thePAMPs that trigger this phenomenon. However, we acknowledged whether this event couldbe triggered in other cells relevant during Ba infection. Here, we demonstrate that Ba RNAreduced the surface expression of MHC-I induced by IFN-γ in the human bronchial epithelium(Calu-6), the human alveolar epithelium (A-549) and the endothelial microvasculature(HMEC) cell lines. In Calu-6 and HMEC cells, Ba RNA induces the retention of MHC-I in theGA. This phenomenon was not observed in A-549 cells. We then evaluated the effect of BaRNA on the secretion of IL-8, IL-6 and MCP-1, key cytokines in Ba infection. Contrary to ourexpectations, HMEC, Calu-6 and A-549 cells treated with Ba RNA had higher IL-8 and IL-6levels compared to untreated cells. In addition, we showed that Ba RNA down-modulatesthe MHC-I surface expression induced by IFN-γ on human monocytes/macrophages via thepathway of the Epidermal Growth Factor Receptor (EGFR). So, cells were stimulated withan EGFR ligand-blocking antibody (Cetuximab) and Ba RNA. Neutralization of the EGFR tosome extent reversed the down-modulation of MHC-I mediated by Ba RNA in HMEC and A-549 cells. In conclusion, this is the first study exploring a central immune evasion strategy,such as the downregulation of MHC-I surface expression, beyond monocytes and couldshed light on how it persists effectively within the host, enduring unseen and escaping CD8+T cell surveillance.
publishDate 2024
dc.date.none.fl_str_mv 2024-07
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/11336/240939
Serafino, Agustina; Bertinat, Yasmín Ayelén; Bueno, Jorgelina; Pittaluga, Jose; Birnberg Weiss, Federico; et al.; Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells; Public Library of Science; Plos One; 19; 7; 7-2024; 1-16
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/240939
identifier_str_mv Serafino, Agustina; Bertinat, Yasmín Ayelén; Bueno, Jorgelina; Pittaluga, Jose; Birnberg Weiss, Federico; et al.; Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells; Public Library of Science; Plos One; 19; 7; 7-2024; 1-16
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.pone.0306429
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0306429
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613568858685440
score 13.070432

Publicaciones similares