B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes

Autores
Milillo, María Ayelén; Velasquez, Lis Noelia; Trotta, Aldana; Delpino, María Victoria; Balboa, Luciana; Giambartolomei, Guillermo Hernan; Barrionuevo, Paula
Año de publicación
2016
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Brucella abortus elicits a strong Th1 immune response whichactivates cytotoxic T lymphocytes. However, this pathogen is ableto survive inside macrophages and generate a chronic infection.Previously we reported that infection of human monocytes/macrophageswith B. abortus inhibits the IFN-γ-induced MHC-I cellsurface expression. More importantly, we have recently demonstratedthat B. abortus RNA, described as a viability-associated(vita)-PAMP, is the bacterial component involved in this phenomenon.Thus, the aim of this study was to further characterize thecomponent, signalling pathways and mechanisms implicated inMHC-I down-modulation. For this, RNases-treated B. abortus RNAwas employed to stimulate human monocytic THP-1 cells in thepresence of IFN-γ for 48 h. Then, the expression of MHC-I moleculeswas evaluated by flow cytometry. Surprisingly, completelydegraded RNA was still able to inhibit MHC-I expression (p<0.05)and it also induced the intracellular retention of these moleculeswithin the Golgi apparatus into the same extent as intact RNA. Onthe contrary, DNase- and Proteinase K-treated RNA as well aseukaryotic RNA controls elicited no effect. Furthermore, B. abortusRNA also inhibited MCH-I expression on human primary monocytesand murine bone-marrow derived macrophages (p<0.05).TLR3 is one of the best known RNA immune receptors, thereforewe evaluated whether it could be involved in this phenomenon.Yet, in the presence of a TLR3 inhibitor, B. abortus RNA downregulated MHC-I expression. On the other hand, neutralization ofthe EGFR resulted in partial recovery (p<0.05) of RNA-mediatedMHC-I inhibition. Overall, these results indicate that the vita-PAMP RNA as well as its degradation products constitute a novelvirulence factor whereby B. abortus, by a TLR3 independentmechanism and through the EGFR pathway, inhibit MHC-I expression.Thus, bacteria can hide within infected cells and avoid theimmunological surveillance of cytotoxic CD8+ T cells.
Fil: Milillo, María 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: Velasquez, Lis Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Trotta, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; 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
LXI Reunión Anual de la Sociedad Agentina de Investigación Clínica; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; VII Reunión Anual de la Sociedad Argentina de Nanomedicina y V Congreso Nacional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Farmacología Experimental
Sociedad Argentina de Nanomedicina
Asociación Argentina De Ciencia y Tecnología De Animales De Laboratorio
Materia
RNA
BRUCELLA
MHC-I
MACROPHAGE
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:11336/242543
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/242543
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytesMilillo, María AyelénVelasquez, Lis NoeliaTrotta, AldanaDelpino, María VictoriaBalboa, LucianaGiambartolomei, Guillermo HernanBarrionuevo, PaulaRNABRUCELLAMHC-IMACROPHAGEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Brucella abortus elicits a strong Th1 immune response whichactivates cytotoxic T lymphocytes. However, this pathogen is ableto survive inside macrophages and generate a chronic infection.Previously we reported that infection of human monocytes/macrophageswith B. abortus inhibits the IFN-γ-induced MHC-I cellsurface expression. More importantly, we have recently demonstratedthat B. abortus RNA, described as a viability-associated(vita)-PAMP, is the bacterial component involved in this phenomenon.Thus, the aim of this study was to further characterize thecomponent, signalling pathways and mechanisms implicated inMHC-I down-modulation. For this, RNases-treated B. abortus RNAwas employed to stimulate human monocytic THP-1 cells in thepresence of IFN-γ for 48 h. Then, the expression of MHC-I moleculeswas evaluated by flow cytometry. Surprisingly, completelydegraded RNA was still able to inhibit MHC-I expression (p<0.05)and it also induced the intracellular retention of these moleculeswithin the Golgi apparatus into the same extent as intact RNA. Onthe contrary, DNase- and Proteinase K-treated RNA as well aseukaryotic RNA controls elicited no effect. Furthermore, B. abortusRNA also inhibited MCH-I expression on human primary monocytesand murine bone-marrow derived macrophages (p<0.05).TLR3 is one of the best known RNA immune receptors, thereforewe evaluated whether it could be involved in this phenomenon.Yet, in the presence of a TLR3 inhibitor, B. abortus RNA downregulated MHC-I expression. On the other hand, neutralization ofthe EGFR resulted in partial recovery (p<0.05) of RNA-mediatedMHC-I inhibition. Overall, these results indicate that the vita-PAMP RNA as well as its degradation products constitute a novelvirulence factor whereby B. abortus, by a TLR3 independentmechanism and through the EGFR pathway, inhibit MHC-I expression.Thus, bacteria can hide within infected cells and avoid theimmunological surveillance of cytotoxic CD8+ T cells.Fil: Milillo, María Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Velasquez, Lis Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Trotta, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; 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; ArgentinaLXI Reunión Anual de la Sociedad Agentina de Investigación Clínica; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; VII Reunión Anual de la Sociedad Argentina de Nanomedicina y V Congreso Nacional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de Farmacología ExperimentalSociedad Argentina de NanomedicinaAsociación Argentina De Ciencia y Tecnología De Animales De LaboratorioFundación Revista Medicina2016info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/242543B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes; LXI Reunión Anual de la Sociedad Agentina de Investigación Clínica; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; VII Reunión Anual de la Sociedad Argentina de Nanomedicina y V Congreso Nacional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2016; 1-21669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/reunion-anualInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:50:35Zoai:ri.conicet.gov.ar:11336/242543instacron: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:34982025-10-15 14:50:35.421CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes
title B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes
spellingShingle B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes
Milillo, María Ayelén
RNA
BRUCELLA
MHC-I
MACROPHAGE
title_short B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes
title_full B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes
title_fullStr B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes
title_full_unstemmed B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes
title_sort B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes
dc.creator.none.fl_str_mv Milillo, María Ayelén
Velasquez, Lis Noelia
Trotta, Aldana
Delpino, María Victoria
Balboa, Luciana
Giambartolomei, Guillermo Hernan
Barrionuevo, Paula
author Milillo, María Ayelén
author_facet Milillo, María Ayelén
Velasquez, Lis Noelia
Trotta, Aldana
Delpino, María Victoria
Balboa, Luciana
Giambartolomei, Guillermo Hernan
Barrionuevo, Paula
author_role author
author2 Velasquez, Lis Noelia
Trotta, Aldana
Delpino, María Victoria
Balboa, Luciana
Giambartolomei, Guillermo Hernan
Barrionuevo, Paula
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv RNA
BRUCELLA
MHC-I
MACROPHAGE
topic RNA
BRUCELLA
MHC-I
MACROPHAGE
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 elicits a strong Th1 immune response whichactivates cytotoxic T lymphocytes. However, this pathogen is ableto survive inside macrophages and generate a chronic infection.Previously we reported that infection of human monocytes/macrophageswith B. abortus inhibits the IFN-γ-induced MHC-I cellsurface expression. More importantly, we have recently demonstratedthat B. abortus RNA, described as a viability-associated(vita)-PAMP, is the bacterial component involved in this phenomenon.Thus, the aim of this study was to further characterize thecomponent, signalling pathways and mechanisms implicated inMHC-I down-modulation. For this, RNases-treated B. abortus RNAwas employed to stimulate human monocytic THP-1 cells in thepresence of IFN-γ for 48 h. Then, the expression of MHC-I moleculeswas evaluated by flow cytometry. Surprisingly, completelydegraded RNA was still able to inhibit MHC-I expression (p<0.05)and it also induced the intracellular retention of these moleculeswithin the Golgi apparatus into the same extent as intact RNA. Onthe contrary, DNase- and Proteinase K-treated RNA as well aseukaryotic RNA controls elicited no effect. Furthermore, B. abortusRNA also inhibited MCH-I expression on human primary monocytesand murine bone-marrow derived macrophages (p<0.05).TLR3 is one of the best known RNA immune receptors, thereforewe evaluated whether it could be involved in this phenomenon.Yet, in the presence of a TLR3 inhibitor, B. abortus RNA downregulated MHC-I expression. On the other hand, neutralization ofthe EGFR resulted in partial recovery (p<0.05) of RNA-mediatedMHC-I inhibition. Overall, these results indicate that the vita-PAMP RNA as well as its degradation products constitute a novelvirulence factor whereby B. abortus, by a TLR3 independentmechanism and through the EGFR pathway, inhibit MHC-I expression.Thus, bacteria can hide within infected cells and avoid theimmunological surveillance of cytotoxic CD8+ T cells.
Fil: Milillo, María 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: Velasquez, Lis Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Trotta, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; 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
LXI Reunión Anual de la Sociedad Agentina de Investigación Clínica; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; VII Reunión Anual de la Sociedad Argentina de Nanomedicina y V Congreso Nacional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Farmacología Experimental
Sociedad Argentina de Nanomedicina
Asociación Argentina De Ciencia y Tecnología De Animales De Laboratorio
description Brucella abortus elicits a strong Th1 immune response whichactivates cytotoxic T lymphocytes. However, this pathogen is ableto survive inside macrophages and generate a chronic infection.Previously we reported that infection of human monocytes/macrophageswith B. abortus inhibits the IFN-γ-induced MHC-I cellsurface expression. More importantly, we have recently demonstratedthat B. abortus RNA, described as a viability-associated(vita)-PAMP, is the bacterial component involved in this phenomenon.Thus, the aim of this study was to further characterize thecomponent, signalling pathways and mechanisms implicated inMHC-I down-modulation. For this, RNases-treated B. abortus RNAwas employed to stimulate human monocytic THP-1 cells in thepresence of IFN-γ for 48 h. Then, the expression of MHC-I moleculeswas evaluated by flow cytometry. Surprisingly, completelydegraded RNA was still able to inhibit MHC-I expression (p<0.05)and it also induced the intracellular retention of these moleculeswithin the Golgi apparatus into the same extent as intact RNA. Onthe contrary, DNase- and Proteinase K-treated RNA as well aseukaryotic RNA controls elicited no effect. Furthermore, B. abortusRNA also inhibited MCH-I expression on human primary monocytesand murine bone-marrow derived macrophages (p<0.05).TLR3 is one of the best known RNA immune receptors, thereforewe evaluated whether it could be involved in this phenomenon.Yet, in the presence of a TLR3 inhibitor, B. abortus RNA downregulated MHC-I expression. On the other hand, neutralization ofthe EGFR resulted in partial recovery (p<0.05) of RNA-mediatedMHC-I inhibition. Overall, these results indicate that the vita-PAMP RNA as well as its degradation products constitute a novelvirulence factor whereby B. abortus, by a TLR3 independentmechanism and through the EGFR pathway, inhibit MHC-I expression.Thus, bacteria can hide within infected cells and avoid theimmunological surveillance of cytotoxic CD8+ T cells.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/242543
B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes; LXI Reunión Anual de la Sociedad Agentina de Investigación Clínica; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; VII Reunión Anual de la Sociedad Argentina de Nanomedicina y V Congreso Nacional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2016; 1-2
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/242543
identifier_str_mv B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes; LXI Reunión Anual de la Sociedad Agentina de Investigación Clínica; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; VII Reunión Anual de la Sociedad Argentina de Nanomedicina y V Congreso Nacional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2016; 1-2
1669-9106
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://www.saic.org.ar/reunion-anual
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
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dc.format.none.fl_str_mv application/pdf
application/pdf
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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
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