Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK

Autores
Balboa, Luciana; Romero, María Mercedes; Laborde, Evangelina Andrea; Sabio y García, Carmen Alejandra; Basile, Juan Ignacio; Schierloh, Luis Pablo; Yokobori, Noemí; Musella, Rosa María; Castagnino, Jorge; de la Barrera, Silvia Susana; Sasiain, María del Carmen; Alemán, Mercedes
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Tuberculosis (TB) is one of the world´s most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16+/CD16− Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16− Mos differentiated into CD1a+DC-SIGNhigh cells achieving an efficient recall response, while CD16+ Mos differentiated into a CD1a−DC-SIGNlow population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16+ Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16− Mo differentiation. Furthermore, depletion of CD16+ Mos indeed improved the differentiation of Mos from TB patients toward CD1a+DC-SIGNhigh DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16+ Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs.
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: Romero, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Laborde, Evangelina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Sabio y García, Carmen Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Basile, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Yokobori, Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Castagnino, Jorge. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Alemán, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
Dendritic Cells
Monocyte Differentiation
Tuberculosis
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:11336/20804

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network_name_str CONICET Digital (CONICET)
spelling Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPKBalboa, LucianaRomero, María MercedesLaborde, Evangelina AndreaSabio y García, Carmen AlejandraBasile, Juan IgnacioSchierloh, Luis PabloYokobori, NoemíMusella, Rosa MaríaCastagnino, Jorgede la Barrera, Silvia SusanaSasiain, María del CarmenAlemán, MercedesDendritic CellsMonocyte DifferentiationTuberculosishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Tuberculosis (TB) is one of the world´s most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16+/CD16− Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16− Mos differentiated into CD1a+DC-SIGNhigh cells achieving an efficient recall response, while CD16+ Mos differentiated into a CD1a−DC-SIGNlow population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16+ Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16− Mo differentiation. Furthermore, depletion of CD16+ Mos indeed improved the differentiation of Mos from TB patients toward CD1a+DC-SIGNhigh DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16+ Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs.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; ArgentinaFil: Romero, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Laborde, Evangelina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Sabio y García, Carmen Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Basile, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Yokobori, Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Castagnino, Jorge. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Alemán, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaWiley VCH Verlag2013-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/20804Balboa, Luciana; Romero, María Mercedes; Laborde, Evangelina Andrea; Sabio y García, Carmen Alejandra; Basile, Juan Ignacio; et al.; Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK; Wiley VCH Verlag; European Journal of Immunology; 43; 2; 2-2013; 335-3470014-29801521-4141CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/eji.201242557/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1002/eji.201242557info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:33Zoai:ri.conicet.gov.ar:11336/20804instacron: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:34982025-09-03 09:48:34.115CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK
title Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK
spellingShingle Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK
Balboa, Luciana
Dendritic Cells
Monocyte Differentiation
Tuberculosis
title_short Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK
title_full Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK
title_fullStr Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK
title_full_unstemmed Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK
title_sort Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK
dc.creator.none.fl_str_mv Balboa, Luciana
Romero, María Mercedes
Laborde, Evangelina Andrea
Sabio y García, Carmen Alejandra
Basile, Juan Ignacio
Schierloh, Luis Pablo
Yokobori, Noemí
Musella, Rosa María
Castagnino, Jorge
de la Barrera, Silvia Susana
Sasiain, María del Carmen
Alemán, Mercedes
author Balboa, Luciana
author_facet Balboa, Luciana
Romero, María Mercedes
Laborde, Evangelina Andrea
Sabio y García, Carmen Alejandra
Basile, Juan Ignacio
Schierloh, Luis Pablo
Yokobori, Noemí
Musella, Rosa María
Castagnino, Jorge
de la Barrera, Silvia Susana
Sasiain, María del Carmen
Alemán, Mercedes
author_role author
author2 Romero, María Mercedes
Laborde, Evangelina Andrea
Sabio y García, Carmen Alejandra
Basile, Juan Ignacio
Schierloh, Luis Pablo
Yokobori, Noemí
Musella, Rosa María
Castagnino, Jorge
de la Barrera, Silvia Susana
Sasiain, María del Carmen
Alemán, Mercedes
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Dendritic Cells
Monocyte Differentiation
Tuberculosis
topic Dendritic Cells
Monocyte Differentiation
Tuberculosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Tuberculosis (TB) is one of the world´s most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16+/CD16− Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16− Mos differentiated into CD1a+DC-SIGNhigh cells achieving an efficient recall response, while CD16+ Mos differentiated into a CD1a−DC-SIGNlow population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16+ Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16− Mo differentiation. Furthermore, depletion of CD16+ Mos indeed improved the differentiation of Mos from TB patients toward CD1a+DC-SIGNhigh DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16+ Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs.
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: Romero, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Laborde, Evangelina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Sabio y García, Carmen Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Basile, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Yokobori, Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Castagnino, Jorge. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Alemán, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Tuberculosis (TB) is one of the world´s most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16+/CD16− Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16− Mos differentiated into CD1a+DC-SIGNhigh cells achieving an efficient recall response, while CD16+ Mos differentiated into a CD1a−DC-SIGNlow population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16+ Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16− Mo differentiation. Furthermore, depletion of CD16+ Mos indeed improved the differentiation of Mos from TB patients toward CD1a+DC-SIGNhigh DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16+ Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs.
publishDate 2013
dc.date.none.fl_str_mv 2013-02
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/11336/20804
Balboa, Luciana; Romero, María Mercedes; Laborde, Evangelina Andrea; Sabio y García, Carmen Alejandra; Basile, Juan Ignacio; et al.; Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK; Wiley VCH Verlag; European Journal of Immunology; 43; 2; 2-2013; 335-347
0014-2980
1521-4141
CONICET Digital
CONICET
url http://hdl.handle.net/11336/20804
identifier_str_mv Balboa, Luciana; Romero, María Mercedes; Laborde, Evangelina Andrea; Sabio y García, Carmen Alejandra; Basile, Juan Ignacio; et al.; Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK; Wiley VCH Verlag; European Journal of Immunology; 43; 2; 2-2013; 335-347
0014-2980
1521-4141
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/eji.201242557/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1002/eji.201242557
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
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
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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