Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages

Autores
Ferrero, Mariana Cristina; Hielpos, María Soledad; Carvalho, Natalia; Barrionuevo, Paula; Corsetti, Patricia; Giambartolomei, Guillermo Hernan; Costa Oliveira, Sergio; Baldi, Pablo Cesar
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alveolar macrophages (AM) seem to constitute the main cellular target of inhaled brucellae. Here we show that Brucella abortus invades and replicates in murine AM without inducing cytotoxicity. B. abortus infection induced a statistically significant increase of TNF-α, KC, IL-1β, IL-6 and IL-12 in AM from C57BL/6 mice and Balb/c mice, but these responses were generally weaker and/or delayed as compared to those elicited in peritoneal macrophages. Studies using knockout mice for TLR2, TLR4 and TLR9 revealed that TNF-α and KC responses were mediated by TLR2 recognition. Brucella infection reduced in a MOI-dependent manner the expression of MHC-II molecules induced by gamma-interferon (IFN-γ) in AM. The same phenomenon was induced by incubation with heat-killed B. abortus (HKBA) or the lipidated form of the 19 kDa outer membrane protein of Brucella (L-Omp19), and was shown to be mediated by TLR2 recognition. In contrast, no significant down-regulation of MHC-II was induced by either unlipidated Omp19 or Brucella LPS. In a functional assay, treatment of AM with either L-Omp19 or HKBA reduced the MHC-II-restricted presentation of OVA peptides to specific T cells. One week after intra-tracheal infection viable B. abortus was detected in AM from both wild type and TLR2 KO mice, but CFU counts were higher in the latter. These results suggest that B. abortus may survive in AM after inhalatory infection in spite of a certain degree of immune control exerted by the TLR2-mediated inflammatory response. Both the modest nature of the latter and the modulation of MHC-II expression by the bacterium may contribute to such survival.
Fil: Ferrero, Mariana Cristina. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Hielpos, María Soledad. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Carvalho, Natalia. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; Brasil
Fil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Corsetti, Patricia. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; Brasil
Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Costa Oliveira, Sergio. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; Brasil
Fil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Materia
Brucella
Alveolar Macrophages
Innate Immunity
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:11336/8035
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophagesFerrero, Mariana CristinaHielpos, María SoledadCarvalho, NataliaBarrionuevo, PaulaCorsetti, PatriciaGiambartolomei, Guillermo HernanCosta Oliveira, SergioBaldi, Pablo CesarBrucellaAlveolar MacrophagesInnate Immunityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Alveolar macrophages (AM) seem to constitute the main cellular target of inhaled brucellae. Here we show that Brucella abortus invades and replicates in murine AM without inducing cytotoxicity. B. abortus infection induced a statistically significant increase of TNF-α, KC, IL-1β, IL-6 and IL-12 in AM from C57BL/6 mice and Balb/c mice, but these responses were generally weaker and/or delayed as compared to those elicited in peritoneal macrophages. Studies using knockout mice for TLR2, TLR4 and TLR9 revealed that TNF-α and KC responses were mediated by TLR2 recognition. Brucella infection reduced in a MOI-dependent manner the expression of MHC-II molecules induced by gamma-interferon (IFN-γ) in AM. The same phenomenon was induced by incubation with heat-killed B. abortus (HKBA) or the lipidated form of the 19 kDa outer membrane protein of Brucella (L-Omp19), and was shown to be mediated by TLR2 recognition. In contrast, no significant down-regulation of MHC-II was induced by either unlipidated Omp19 or Brucella LPS. In a functional assay, treatment of AM with either L-Omp19 or HKBA reduced the MHC-II-restricted presentation of OVA peptides to specific T cells. One week after intra-tracheal infection viable B. abortus was detected in AM from both wild type and TLR2 KO mice, but CFU counts were higher in the latter. These results suggest that B. abortus may survive in AM after inhalatory infection in spite of a certain degree of immune control exerted by the TLR2-mediated inflammatory response. Both the modest nature of the latter and the modulation of MHC-II expression by the bacterium may contribute to such survival.Fil: Ferrero, Mariana Cristina. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Hielpos, María Soledad. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Carvalho, Natalia. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Corsetti, Patricia. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Costa Oliveira, Sergio. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaAmerican Society For Microbiology2014-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8035Ferrero, Mariana Cristina; Hielpos, María Soledad; Carvalho, Natalia; Barrionuevo, Paula; Corsetti, Patricia; et al.; Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages; American Society For Microbiology; Infection And Immunity; 82; 2; 2-2014; 626-6390019-9567enginfo:eu-repo/semantics/altIdentifier/url/http://iai.asm.org/content/82/2/626.fullinfo:eu-repo/semantics/altIdentifier/doi/10.1128/IAI.01237-13info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:47:01Zoai:ri.conicet.gov.ar:11336/8035instacron: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 14:47:01.86CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages
title Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages
spellingShingle Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages
Ferrero, Mariana Cristina
Brucella
Alveolar Macrophages
Innate Immunity
title_short Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages
title_full Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages
title_fullStr Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages
title_full_unstemmed Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages
title_sort Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages
dc.creator.none.fl_str_mv Ferrero, Mariana Cristina
Hielpos, María Soledad
Carvalho, Natalia
Barrionuevo, Paula
Corsetti, Patricia
Giambartolomei, Guillermo Hernan
Costa Oliveira, Sergio
Baldi, Pablo Cesar
author Ferrero, Mariana Cristina
author_facet Ferrero, Mariana Cristina
Hielpos, María Soledad
Carvalho, Natalia
Barrionuevo, Paula
Corsetti, Patricia
Giambartolomei, Guillermo Hernan
Costa Oliveira, Sergio
Baldi, Pablo Cesar
author_role author
author2 Hielpos, María Soledad
Carvalho, Natalia
Barrionuevo, Paula
Corsetti, Patricia
Giambartolomei, Guillermo Hernan
Costa Oliveira, Sergio
Baldi, Pablo Cesar
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Brucella
Alveolar Macrophages
Innate Immunity
topic Brucella
Alveolar Macrophages
Innate Immunity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alveolar macrophages (AM) seem to constitute the main cellular target of inhaled brucellae. Here we show that Brucella abortus invades and replicates in murine AM without inducing cytotoxicity. B. abortus infection induced a statistically significant increase of TNF-α, KC, IL-1β, IL-6 and IL-12 in AM from C57BL/6 mice and Balb/c mice, but these responses were generally weaker and/or delayed as compared to those elicited in peritoneal macrophages. Studies using knockout mice for TLR2, TLR4 and TLR9 revealed that TNF-α and KC responses were mediated by TLR2 recognition. Brucella infection reduced in a MOI-dependent manner the expression of MHC-II molecules induced by gamma-interferon (IFN-γ) in AM. The same phenomenon was induced by incubation with heat-killed B. abortus (HKBA) or the lipidated form of the 19 kDa outer membrane protein of Brucella (L-Omp19), and was shown to be mediated by TLR2 recognition. In contrast, no significant down-regulation of MHC-II was induced by either unlipidated Omp19 or Brucella LPS. In a functional assay, treatment of AM with either L-Omp19 or HKBA reduced the MHC-II-restricted presentation of OVA peptides to specific T cells. One week after intra-tracheal infection viable B. abortus was detected in AM from both wild type and TLR2 KO mice, but CFU counts were higher in the latter. These results suggest that B. abortus may survive in AM after inhalatory infection in spite of a certain degree of immune control exerted by the TLR2-mediated inflammatory response. Both the modest nature of the latter and the modulation of MHC-II expression by the bacterium may contribute to such survival.
Fil: Ferrero, Mariana Cristina. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Hielpos, María Soledad. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
Fil: Carvalho, Natalia. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; Brasil
Fil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Corsetti, Patricia. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; Brasil
Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Costa Oliveira, Sergio. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; Brasil
Fil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina
description Alveolar macrophages (AM) seem to constitute the main cellular target of inhaled brucellae. Here we show that Brucella abortus invades and replicates in murine AM without inducing cytotoxicity. B. abortus infection induced a statistically significant increase of TNF-α, KC, IL-1β, IL-6 and IL-12 in AM from C57BL/6 mice and Balb/c mice, but these responses were generally weaker and/or delayed as compared to those elicited in peritoneal macrophages. Studies using knockout mice for TLR2, TLR4 and TLR9 revealed that TNF-α and KC responses were mediated by TLR2 recognition. Brucella infection reduced in a MOI-dependent manner the expression of MHC-II molecules induced by gamma-interferon (IFN-γ) in AM. The same phenomenon was induced by incubation with heat-killed B. abortus (HKBA) or the lipidated form of the 19 kDa outer membrane protein of Brucella (L-Omp19), and was shown to be mediated by TLR2 recognition. In contrast, no significant down-regulation of MHC-II was induced by either unlipidated Omp19 or Brucella LPS. In a functional assay, treatment of AM with either L-Omp19 or HKBA reduced the MHC-II-restricted presentation of OVA peptides to specific T cells. One week after intra-tracheal infection viable B. abortus was detected in AM from both wild type and TLR2 KO mice, but CFU counts were higher in the latter. These results suggest that B. abortus may survive in AM after inhalatory infection in spite of a certain degree of immune control exerted by the TLR2-mediated inflammatory response. Both the modest nature of the latter and the modulation of MHC-II expression by the bacterium may contribute to such survival.
publishDate 2014
dc.date.none.fl_str_mv 2014-02
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/11336/8035
Ferrero, Mariana Cristina; Hielpos, María Soledad; Carvalho, Natalia; Barrionuevo, Paula; Corsetti, Patricia; et al.; Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages; American Society For Microbiology; Infection And Immunity; 82; 2; 2-2014; 626-639
0019-9567
url http://hdl.handle.net/11336/8035
identifier_str_mv Ferrero, Mariana Cristina; Hielpos, María Soledad; Carvalho, Natalia; Barrionuevo, Paula; Corsetti, Patricia; et al.; Key role of TLR2 in the inflammatory response and MHC-II down-regulation in Brucella-infected alveolar macrophages; American Society For Microbiology; Infection And Immunity; 82; 2; 2-2014; 626-639
0019-9567
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://iai.asm.org/content/82/2/626.full
info:eu-repo/semantics/altIdentifier/doi/10.1128/IAI.01237-13
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society For Microbiology
publisher.none.fl_str_mv American Society For Microbiology
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
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