CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis

Autores
Fernández Do Porto, Darío Augusto; Jurado, Javier Oscar; Pasquinelli, Virginia; Alvarez, Ivana Belén; Aspera, Romina Haydeé; Musella, Rosa María; García, Verónica Edith
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Protective immunity against Mycobacterium tuberculosis is primarily mediated by the interaction of antigen-specific T cells and antigen presenting cells, which often depends on the interplay of cytokines produced by these cells. Costimulatory signals represent a complex network of receptor-ligand interactions that qualitatively and quantitatively influence immune responses. Thus, here we investigated the function of CD137 and CD137L, molecules known to have a central role in immune regulation, during human tuberculosis (TB). We demonstrated that M. tuberculosis antigen stimulation increased both CD137 and CD137L expression on monocytes and NK cells from TB patients and healthy donors, but only up-regulated CD137 on T lymphocytes. Blockage of the CD137 pathway enhanced the levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by monocytes and NK against M. tuberculosis. In contrast, CD137 blockage significantly decreased the specific degranulation of CD8 + T cells and the percentage of specific IFN-γ and TNF-α producing lymphocytes against the pathogen. Furthermore, inhibition of the CD137 pathway markedly increased T-cell apoptosis. Taken together, our results demonstrate that CD137:CD137L interactions regulate the innate and adaptive immune response of the host against M. tuberculosis. © 2012 Australasian Society for Immunology Inc. All rights reserved.
Fil: Fernández Do Porto, Darío Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Jurado, Javier Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Pasquinelli, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Alvarez, Ivana Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Aspera, Romina Haydeé. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Materia
CD137
CYTOKINES
MONOCYTES
NK CELLS
T CELLS
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:11336/66682
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/66682
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosisFernández Do Porto, Darío AugustoJurado, Javier OscarPasquinelli, VirginiaAlvarez, Ivana BelénAspera, Romina HaydeéMusella, Rosa MaríaGarcía, Verónica EdithCD137CYTOKINESMONOCYTESNK CELLST CELLSTUBERCULOSIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Protective immunity against Mycobacterium tuberculosis is primarily mediated by the interaction of antigen-specific T cells and antigen presenting cells, which often depends on the interplay of cytokines produced by these cells. Costimulatory signals represent a complex network of receptor-ligand interactions that qualitatively and quantitatively influence immune responses. Thus, here we investigated the function of CD137 and CD137L, molecules known to have a central role in immune regulation, during human tuberculosis (TB). We demonstrated that M. tuberculosis antigen stimulation increased both CD137 and CD137L expression on monocytes and NK cells from TB patients and healthy donors, but only up-regulated CD137 on T lymphocytes. Blockage of the CD137 pathway enhanced the levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by monocytes and NK against M. tuberculosis. In contrast, CD137 blockage significantly decreased the specific degranulation of CD8 + T cells and the percentage of specific IFN-γ and TNF-α producing lymphocytes against the pathogen. Furthermore, inhibition of the CD137 pathway markedly increased T-cell apoptosis. Taken together, our results demonstrate that CD137:CD137L interactions regulate the innate and adaptive immune response of the host against M. tuberculosis. © 2012 Australasian Society for Immunology Inc. All rights reserved.Fil: Fernández Do Porto, Darío Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Jurado, Javier Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Pasquinelli, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Alvarez, Ivana Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Aspera, Romina Haydeé. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaNature Publishing Group2012-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66682Fernández Do Porto, Darío Augusto; Jurado, Javier Oscar; Pasquinelli, Virginia; Alvarez, Ivana Belén; Aspera, Romina Haydeé; et al.; CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis; Nature Publishing Group; Immunology and Cell Biology; 90; 4; 4-2012; 449-4560818-9641CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/icb.2011.63info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1038/icb.2011.63info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:29Zoai:ri.conicet.gov.ar:11336/66682instacron: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 09:51:29.706CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis
title CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis
spellingShingle CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis
Fernández Do Porto, Darío Augusto
CD137
CYTOKINES
MONOCYTES
NK CELLS
T CELLS
TUBERCULOSIS
title_short CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis
title_full CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis
title_fullStr CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis
title_full_unstemmed CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis
title_sort CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis
dc.creator.none.fl_str_mv Fernández Do Porto, Darío Augusto
Jurado, Javier Oscar
Pasquinelli, Virginia
Alvarez, Ivana Belén
Aspera, Romina Haydeé
Musella, Rosa María
García, Verónica Edith
author Fernández Do Porto, Darío Augusto
author_facet Fernández Do Porto, Darío Augusto
Jurado, Javier Oscar
Pasquinelli, Virginia
Alvarez, Ivana Belén
Aspera, Romina Haydeé
Musella, Rosa María
García, Verónica Edith
author_role author
author2 Jurado, Javier Oscar
Pasquinelli, Virginia
Alvarez, Ivana Belén
Aspera, Romina Haydeé
Musella, Rosa María
García, Verónica Edith
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CD137
CYTOKINES
MONOCYTES
NK CELLS
T CELLS
TUBERCULOSIS
topic CD137
CYTOKINES
MONOCYTES
NK CELLS
T CELLS
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 Protective immunity against Mycobacterium tuberculosis is primarily mediated by the interaction of antigen-specific T cells and antigen presenting cells, which often depends on the interplay of cytokines produced by these cells. Costimulatory signals represent a complex network of receptor-ligand interactions that qualitatively and quantitatively influence immune responses. Thus, here we investigated the function of CD137 and CD137L, molecules known to have a central role in immune regulation, during human tuberculosis (TB). We demonstrated that M. tuberculosis antigen stimulation increased both CD137 and CD137L expression on monocytes and NK cells from TB patients and healthy donors, but only up-regulated CD137 on T lymphocytes. Blockage of the CD137 pathway enhanced the levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by monocytes and NK against M. tuberculosis. In contrast, CD137 blockage significantly decreased the specific degranulation of CD8 + T cells and the percentage of specific IFN-γ and TNF-α producing lymphocytes against the pathogen. Furthermore, inhibition of the CD137 pathway markedly increased T-cell apoptosis. Taken together, our results demonstrate that CD137:CD137L interactions regulate the innate and adaptive immune response of the host against M. tuberculosis. © 2012 Australasian Society for Immunology Inc. All rights reserved.
Fil: Fernández Do Porto, Darío Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Jurado, Javier Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Pasquinelli, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Alvarez, Ivana Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Aspera, Romina Haydeé. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
description Protective immunity against Mycobacterium tuberculosis is primarily mediated by the interaction of antigen-specific T cells and antigen presenting cells, which often depends on the interplay of cytokines produced by these cells. Costimulatory signals represent a complex network of receptor-ligand interactions that qualitatively and quantitatively influence immune responses. Thus, here we investigated the function of CD137 and CD137L, molecules known to have a central role in immune regulation, during human tuberculosis (TB). We demonstrated that M. tuberculosis antigen stimulation increased both CD137 and CD137L expression on monocytes and NK cells from TB patients and healthy donors, but only up-regulated CD137 on T lymphocytes. Blockage of the CD137 pathway enhanced the levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by monocytes and NK against M. tuberculosis. In contrast, CD137 blockage significantly decreased the specific degranulation of CD8 + T cells and the percentage of specific IFN-γ and TNF-α producing lymphocytes against the pathogen. Furthermore, inhibition of the CD137 pathway markedly increased T-cell apoptosis. Taken together, our results demonstrate that CD137:CD137L interactions regulate the innate and adaptive immune response of the host against M. tuberculosis. © 2012 Australasian Society for Immunology Inc. All rights reserved.
publishDate 2012
dc.date.none.fl_str_mv 2012-04
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/11336/66682
Fernández Do Porto, Darío Augusto; Jurado, Javier Oscar; Pasquinelli, Virginia; Alvarez, Ivana Belén; Aspera, Romina Haydeé; et al.; CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis; Nature Publishing Group; Immunology and Cell Biology; 90; 4; 4-2012; 449-456
0818-9641
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66682
identifier_str_mv Fernández Do Porto, Darío Augusto; Jurado, Javier Oscar; Pasquinelli, Virginia; Alvarez, Ivana Belén; Aspera, Romina Haydeé; et al.; CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis; Nature Publishing Group; Immunology and Cell Biology; 90; 4; 4-2012; 449-456
0818-9641
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/icb.2011.63
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1038/icb.2011.63
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
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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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