Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium...

Autores
Geffner, Laura; Yokobori, Noemi; Basile, Juan Ignacio; Schierloh, Pablo; Balboa, Luciana; Romero, María Mercedes; Ritacco, Viviana; Vescovo, Marisa; Gonzalez Montaner, Pablo; López, Beatriz; Barrera, Lucía; Alemán, Mercedes; Abbate, Eduardo; Sasiain, María C.; de la Barrera, Silvia
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Geffner, Laura. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Yokobori, Noemi. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Basile, Juan. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Schierloh, Pablo. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Balboa, Luciana. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Mercedes Romero, María. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Ritacco, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: Vescovo, Marisa. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.
Fil: Gonzalez Montaner, Pablo. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.
Fil: López, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: Barrera, Lucía. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: Alemán, Mercedes. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Sasiain, María C. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: de la Barrera, Silvia. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Abbate, Eduardo. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.
In Argentina, multidrug-resistant tuberculosis (MDR-TB) outbreaks emerged among hospitalized patients with AIDS in the early 1990s and thereafter disseminated to the immunocompetent community. Epidemiological, bacteriological, and genotyping data allowed the identification of certain MDR Mycobacterium tuberculosis outbreak strains, such as the so-called strain M of the Haarlem lineage and strain Ra of the Latin America and Mediterranean lineage. In the current study, we evaluated the immune responses induced by strains M and Ra in peripheral blood mononuclear cells from patients with active MDR-TB or fully drug-susceptible tuberculosis (S-TB) and in purified protein derivative-positive healthy controls (group N). Our results demonstrated that strain M was a weaker gamma interferon (IFN-gamma) inducer than H37Rv for group N. Strain M induced the highest interleukin-4 expression in CD4(+) and CD8(+) T cells from MDR-and S-TB patients, along with the lowest cytotoxic T-lymphocyte (CTL) activity in patients and controls. Hence, impairment of CTL activity is a hallmark of strain M and could be an evasion mechanism employed by this strain to avoid the killing of macrophages by M-specific CTL effectors. In addition, MDR-TB patients had an increased proportion of circulating regulatory T cells (Treg cells), and these cells were further expanded upon in vitro M. tuberculosis stimulation. Experimental Treg cell depletion increased IFN-gamma expression and CTL activity in TB patients, with M-and Ra-induced CTL responses remaining low in MDR-TB patients. Altogether, these results suggest that immunity to MDR strains might depend upon a balance between the individual host response and the ability of different M. tuberculosis genotypes to drive Th1 or Th2 profiles.
Fuente
Infection and Immunity 2009;77(11):5025-5034
Materia
Tuberculosis
Mycobacterium tuberculosis
Resistencia a Medicamentos
Nivel de accesibilidad
acceso abierto
Condiciones de uso
Repositorio
Sistema de Gestión del Conocimiento ANLIS MALBRÁN
Institución
Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
OAI Identificador
oai:sgc.anlis.gob.ar:123456789/407
Acceder
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oai_identifier_str oai:sgc.anlis.gob.ar:123456789/407
network_acronym_str SGCANLIS
repository_id_str a
network_name_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
spelling Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra StrainsGeffner, LauraYokobori, NoemiBasile, Juan IgnacioSchierloh, PabloBalboa, LucianaRomero, María MercedesRitacco, VivianaVescovo, MarisaGonzalez Montaner, PabloLópez, BeatrizBarrera, LucíaAlemán, MercedesAbbate, EduardoSasiain, María C.de la Barrera, SilviaTuberculosisMycobacterium tuberculosisResistencia a MedicamentosFil: Geffner, Laura. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Yokobori, Noemi. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Basile, Juan. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Schierloh, Pablo. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Balboa, Luciana. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Mercedes Romero, María. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Ritacco, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Vescovo, Marisa. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.Fil: Gonzalez Montaner, Pablo. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.Fil: López, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Barrera, Lucía. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Alemán, Mercedes. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Sasiain, María C. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: de la Barrera, Silvia. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Abbate, Eduardo. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.In Argentina, multidrug-resistant tuberculosis (MDR-TB) outbreaks emerged among hospitalized patients with AIDS in the early 1990s and thereafter disseminated to the immunocompetent community. Epidemiological, bacteriological, and genotyping data allowed the identification of certain MDR Mycobacterium tuberculosis outbreak strains, such as the so-called strain M of the Haarlem lineage and strain Ra of the Latin America and Mediterranean lineage. In the current study, we evaluated the immune responses induced by strains M and Ra in peripheral blood mononuclear cells from patients with active MDR-TB or fully drug-susceptible tuberculosis (S-TB) and in purified protein derivative-positive healthy controls (group N). Our results demonstrated that strain M was a weaker gamma interferon (IFN-gamma) inducer than H37Rv for group N. Strain M induced the highest interleukin-4 expression in CD4(+) and CD8(+) T cells from MDR-and S-TB patients, along with the lowest cytotoxic T-lymphocyte (CTL) activity in patients and controls. Hence, impairment of CTL activity is a hallmark of strain M and could be an evasion mechanism employed by this strain to avoid the killing of macrophages by M-specific CTL effectors. In addition, MDR-TB patients had an increased proportion of circulating regulatory T cells (Treg cells), and these cells were further expanded upon in vitro M. tuberculosis stimulation. Experimental Treg cell depletion increased IFN-gamma expression and CTL activity in TB patients, with M-and Ra-induced CTL responses remaining low in MDR-TB patients. Altogether, these results suggest that immunity to MDR strains might depend upon a balance between the individual host response and the ability of different M. tuberculosis genotypes to drive Th1 or Th2 profiles.2009-11info:ar-repo/semantics/articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdf0019-9567http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772532/pdf/0224-09.pdfhttp://sgc.anlis.gob.ar/handle/123456789/407Infection and Immunity 2009;77(11):5025-5034reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁNinstname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"instacron:ANLISInfection and Immunityenginfo:eu-repo/semantics/openAccess2025-09-29T14:30:01Zoai:sgc.anlis.gob.ar:123456789/407Institucionalhttp://sgc.anlis.gob.ar/Organismo científico-tecnológicoNo correspondehttp://sgc.anlis.gob.ar/oai/biblioteca@anlis.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:a2025-09-29 14:30:02.202Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"false
dc.title.none.fl_str_mv Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains
title Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains
spellingShingle Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains
Geffner, Laura
Tuberculosis
Mycobacterium tuberculosis
Resistencia a Medicamentos
title_short Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains
title_full Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains
title_fullStr Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains
title_full_unstemmed Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains
title_sort Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains
dc.creator.none.fl_str_mv Geffner, Laura
Yokobori, Noemi
Basile, Juan Ignacio
Schierloh, Pablo
Balboa, Luciana
Romero, María Mercedes
Ritacco, Viviana
Vescovo, Marisa
Gonzalez Montaner, Pablo
López, Beatriz
Barrera, Lucía
Alemán, Mercedes
Abbate, Eduardo
Sasiain, María C.
de la Barrera, Silvia
author Geffner, Laura
author_facet Geffner, Laura
Yokobori, Noemi
Basile, Juan Ignacio
Schierloh, Pablo
Balboa, Luciana
Romero, María Mercedes
Ritacco, Viviana
Vescovo, Marisa
Gonzalez Montaner, Pablo
López, Beatriz
Barrera, Lucía
Alemán, Mercedes
Abbate, Eduardo
Sasiain, María C.
de la Barrera, Silvia
author_role author
author2 Yokobori, Noemi
Basile, Juan Ignacio
Schierloh, Pablo
Balboa, Luciana
Romero, María Mercedes
Ritacco, Viviana
Vescovo, Marisa
Gonzalez Montaner, Pablo
López, Beatriz
Barrera, Lucía
Alemán, Mercedes
Abbate, Eduardo
Sasiain, María C.
de la Barrera, Silvia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tuberculosis
Mycobacterium tuberculosis
Resistencia a Medicamentos
topic Tuberculosis
Mycobacterium tuberculosis
Resistencia a Medicamentos
dc.description.none.fl_txt_mv Fil: Geffner, Laura. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Yokobori, Noemi. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Basile, Juan. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Schierloh, Pablo. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Balboa, Luciana. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Mercedes Romero, María. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Ritacco, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: Vescovo, Marisa. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.
Fil: Gonzalez Montaner, Pablo. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.
Fil: López, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: Barrera, Lucía. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: Alemán, Mercedes. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Sasiain, María C. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: de la Barrera, Silvia. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
Fil: Abbate, Eduardo. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.
In Argentina, multidrug-resistant tuberculosis (MDR-TB) outbreaks emerged among hospitalized patients with AIDS in the early 1990s and thereafter disseminated to the immunocompetent community. Epidemiological, bacteriological, and genotyping data allowed the identification of certain MDR Mycobacterium tuberculosis outbreak strains, such as the so-called strain M of the Haarlem lineage and strain Ra of the Latin America and Mediterranean lineage. In the current study, we evaluated the immune responses induced by strains M and Ra in peripheral blood mononuclear cells from patients with active MDR-TB or fully drug-susceptible tuberculosis (S-TB) and in purified protein derivative-positive healthy controls (group N). Our results demonstrated that strain M was a weaker gamma interferon (IFN-gamma) inducer than H37Rv for group N. Strain M induced the highest interleukin-4 expression in CD4(+) and CD8(+) T cells from MDR-and S-TB patients, along with the lowest cytotoxic T-lymphocyte (CTL) activity in patients and controls. Hence, impairment of CTL activity is a hallmark of strain M and could be an evasion mechanism employed by this strain to avoid the killing of macrophages by M-specific CTL effectors. In addition, MDR-TB patients had an increased proportion of circulating regulatory T cells (Treg cells), and these cells were further expanded upon in vitro M. tuberculosis stimulation. Experimental Treg cell depletion increased IFN-gamma expression and CTL activity in TB patients, with M-and Ra-induced CTL responses remaining low in MDR-TB patients. Altogether, these results suggest that immunity to MDR strains might depend upon a balance between the individual host response and the ability of different M. tuberculosis genotypes to drive Th1 or Th2 profiles.
description Fil: Geffner, Laura. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.
publishDate 2009
dc.date.none.fl_str_mv 2009-11
dc.type.none.fl_str_mv info:ar-repo/semantics/articulo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv 0019-9567
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772532/pdf/0224-09.pdf
http://sgc.anlis.gob.ar/handle/123456789/407
identifier_str_mv 0019-9567
url http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772532/pdf/0224-09.pdf
http://sgc.anlis.gob.ar/handle/123456789/407
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Infection and Immunity
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Infection and Immunity 2009;77(11):5025-5034
reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron:ANLIS
reponame_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
collection Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname_str Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron_str ANLIS
institution ANLIS
repository.name.fl_str_mv Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
repository.mail.fl_str_mv biblioteca@anlis.gov.ar
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score 12.559606

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