Phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to mycobacterium tuberculosis

Immune control of Mycobacterium tuberculosis depends on interferon γ (IFN-γ)-producing CD4+ lymphocytes. Previous studies have shown that T cells from patients with tuberculosis produce less IFN-γ, compared with healthy donors, in response to mycobacterial antigens, although IFN-γ responses to mitog...

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Autores principales: Pasquinelli, Virginia, Alvarez, Ivana Belén, Jurado, Javier Oscar, García, Verónica Edith
Publicado: 2013
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221899_v207_n2_p340_Pasquinelli
http://hdl.handle.net/20.500.12110/paper_00221899_v207_n2_p340_Pasquinelli
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spelling paper:paper_00221899_v207_n2_p340_Pasquinelli2023-06-08T14:47:01Z Phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to mycobacterium tuberculosis Pasquinelli, Virginia Alvarez, Ivana Belén Jurado, Javier Oscar García, Verónica Edith CREB IFN-γ MAPK signaling Tuberculosis gamma interferon mitogen activated protein kinase mitogen activated protein kinase p38 Mycobacterium antigen small interfering RNA tuberculostatic agent acid fast bacterium article CD4+ T lymphocyte enzyme linked immunosorbent assay flow cytometry interferon production lung tuberculosis lymphocyte activation Mycobacterium tuberculosis nonhuman priority journal protein phosphorylation T lymphocyte Western blotting Immune control of Mycobacterium tuberculosis depends on interferon γ (IFN-γ)-producing CD4+ lymphocytes. Previous studies have shown that T cells from patients with tuberculosis produce less IFN-γ, compared with healthy donors, in response to mycobacterial antigens, although IFN-γ responses to mitogens are preserved. In this work, we found that M. tuberculosis-induced IFN-γ production by human T cells correlated with phosphorylation of the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), and p38. Moreover, the majority of IFN-γ-producing T cells expressed signaling lymphocyte activation molecule (SLAM), and SLAM activation further increased ERK phosphorylation. Interestingly, patients with tuberculosis had delayed activation of ERK and p38, and this was most marked in patients with the poorest IFN-γ responses (ie, low responders). Besides, SLAM signaling failed to phosphorylate ERK in low responders. Our findings suggest that activation of p38 and ERK, in part through SLAM, mediates T-cell IFN-γ production in response to M. tuberculosis, a pathway that is defective in patients with tuberculosis. © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. Fil:Pasquinelli, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Alvarez, I.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Jurado, J.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:García, V.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221899_v207_n2_p340_Pasquinelli http://hdl.handle.net/20.500.12110/paper_00221899_v207_n2_p340_Pasquinelli
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic CREB
IFN-γ
MAPK
signaling
Tuberculosis
gamma interferon
mitogen activated protein kinase
mitogen activated protein kinase p38
Mycobacterium antigen
small interfering RNA
tuberculostatic agent
acid fast bacterium
article
CD4+ T lymphocyte
enzyme linked immunosorbent assay
flow cytometry
interferon production
lung tuberculosis
lymphocyte activation
Mycobacterium tuberculosis
nonhuman
priority journal
protein phosphorylation
T lymphocyte
Western blotting
spellingShingle CREB
IFN-γ
MAPK
signaling
Tuberculosis
gamma interferon
mitogen activated protein kinase
mitogen activated protein kinase p38
Mycobacterium antigen
small interfering RNA
tuberculostatic agent
acid fast bacterium
article
CD4+ T lymphocyte
enzyme linked immunosorbent assay
flow cytometry
interferon production
lung tuberculosis
lymphocyte activation
Mycobacterium tuberculosis
nonhuman
priority journal
protein phosphorylation
T lymphocyte
Western blotting
Pasquinelli, Virginia
Alvarez, Ivana Belén
Jurado, Javier Oscar
García, Verónica Edith
Phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to mycobacterium tuberculosis
topic_facet CREB
IFN-γ
MAPK
signaling
Tuberculosis
gamma interferon
mitogen activated protein kinase
mitogen activated protein kinase p38
Mycobacterium antigen
small interfering RNA
tuberculostatic agent
acid fast bacterium
article
CD4+ T lymphocyte
enzyme linked immunosorbent assay
flow cytometry
interferon production
lung tuberculosis
lymphocyte activation
Mycobacterium tuberculosis
nonhuman
priority journal
protein phosphorylation
T lymphocyte
Western blotting
description Immune control of Mycobacterium tuberculosis depends on interferon γ (IFN-γ)-producing CD4+ lymphocytes. Previous studies have shown that T cells from patients with tuberculosis produce less IFN-γ, compared with healthy donors, in response to mycobacterial antigens, although IFN-γ responses to mitogens are preserved. In this work, we found that M. tuberculosis-induced IFN-γ production by human T cells correlated with phosphorylation of the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), and p38. Moreover, the majority of IFN-γ-producing T cells expressed signaling lymphocyte activation molecule (SLAM), and SLAM activation further increased ERK phosphorylation. Interestingly, patients with tuberculosis had delayed activation of ERK and p38, and this was most marked in patients with the poorest IFN-γ responses (ie, low responders). Besides, SLAM signaling failed to phosphorylate ERK in low responders. Our findings suggest that activation of p38 and ERK, in part through SLAM, mediates T-cell IFN-γ production in response to M. tuberculosis, a pathway that is defective in patients with tuberculosis. © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
author Pasquinelli, Virginia
Alvarez, Ivana Belén
Jurado, Javier Oscar
García, Verónica Edith
author_facet Pasquinelli, Virginia
Alvarez, Ivana Belén
Jurado, Javier Oscar
García, Verónica Edith
author_sort Pasquinelli, Virginia
title Phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to mycobacterium tuberculosis
title_short Phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to mycobacterium tuberculosis
title_full Phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to mycobacterium tuberculosis
title_fullStr Phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to mycobacterium tuberculosis
title_full_unstemmed Phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to mycobacterium tuberculosis
title_sort phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to mycobacterium tuberculosis
publishDate 2013
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221899_v207_n2_p340_Pasquinelli
http://hdl.handle.net/20.500.12110/paper_00221899_v207_n2_p340_Pasquinelli
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AT juradojavieroscar phosphorylationofmitogenactivatedproteinkinasescontributestointerferongproductioninresponsetomycobacteriumtuberculosis
AT garciaveronicaedith phosphorylationofmitogenactivatedproteinkinasescontributestointerferongproductioninresponsetomycobacteriumtuberculosis
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