Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation

Toll-like receptors (TLRs) play a crucial role in the recognition of pathogen-derived components as a first line of defense against infections. It has been suggested that depending on the nature of the pathogens, TLRs activation induce a distinct cytokine profile that may contribute to the polarizat...

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Detalles Bibliográficos
Autores: Francisco, Sara, Arranz, Alicia, Merino, Javier, Punzón, Carmen, Perona Abellón, Rosario, Fresno Escudero, Manuel
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/716826
Acceso en línea:http://hdl.handle.net/10486/716826
https://dx.doi.org/10.3389/fimmu.2021.660065
Access Level:acceso abierto
Palabra clave:Macrophages
innate immunity
toll-like receptors
MAPK signaling
cytokines
Biología y Biomedicina / Biología
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spelling Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activationFrancisco, SaraArranz, AliciaMerino, JavierPunzón, CarmenPerona Abellón, RosarioFresno Escudero, ManuelMacrophagesinnate immunitytoll-like receptorsMAPK signalingcytokinesBiología y Biomedicina / BiologíaToll-like receptors (TLRs) play a crucial role in the recognition of pathogen-derived components as a first line of defense against infections. It has been suggested that depending on the nature of the pathogens, TLRs activation induce a distinct cytokine profile that may contribute to the polarization of the acquired immune response. Here, we investigated the early MAPK signaling activation via TLR4 and TLR2 receptors and its impact in differential cytokine profile by macrophages. We found that TLR2 ligands activated MAPKs p38 and ERK earlier compared to the TLR4 ligand LPS in macrophages. Higher IL-10/IL-12 and IL-10/TNF-α ratios were also observed at later time points in response to TLR2 ligands compared to LPS. The results also indicate an earlier activation of the phosphatase MKP-1 and that MKP-1 KO macrophages show a prolongation in p38 phosphorylation in response to TLR2 stimulation. Furthermore, p38 is critical for IL-10 expression in response to TLR2 ligands, which triggers the macrophage change to a M2 and regulatory phenotype in contrast to the M1 phenotype induced by TLR4 activation. Therefore, the early TLR2-mediated p38 induction contributes for the high IL-10 production, likely as a virulence strategy to suppress host Th1 response against certain types of pathogensThis research was funded by grants from European Unión “Host-microbe interactions in Health and disease. Interface with the immune system”. HOMIN - 317057 - FP7-PEOPLE2012-ITN to Diomune and Ministerio de Ciencia e Innovación (SAF2013-42850-R and SAF2016-75988-R), Instituto de salud Carlos III “ (BIOIMID and RD16/0027/0006), Comunidad de Madrid (S2017/BMD-3671. INFLAMUNE-CM) to MF, and Institutional grants from “Fundación Ramón Areces” and “Banco de Santander”Frontiers Media S.ADepartamento de Biología MolecularFacultad de Ciencias20212021-06-21research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/mswordapplication/pdfhttp://hdl.handle.net/10486/716826https://dx.doi.org/10.3389/fimmu.2021.660065reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7168262026-06-23T12:46:27Z
dc.title.none.fl_str_mv Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation
title Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation
spellingShingle Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation
Francisco, Sara
Macrophages
innate immunity
toll-like receptors
MAPK signaling
cytokines
Biología y Biomedicina / Biología
title_short Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation
title_full Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation
title_fullStr Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation
title_full_unstemmed Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation
title_sort Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation
dc.creator.none.fl_str_mv Francisco, Sara
Arranz, Alicia
Merino, Javier
Punzón, Carmen
Perona Abellón, Rosario
Fresno Escudero, Manuel
author Francisco, Sara
author_facet Francisco, Sara
Arranz, Alicia
Merino, Javier
Punzón, Carmen
Perona Abellón, Rosario
Fresno Escudero, Manuel
author_role author
author2 Arranz, Alicia
Merino, Javier
Punzón, Carmen
Perona Abellón, Rosario
Fresno Escudero, Manuel
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Macrophages
innate immunity
toll-like receptors
MAPK signaling
cytokines
Biología y Biomedicina / Biología
topic Macrophages
innate immunity
toll-like receptors
MAPK signaling
cytokines
Biología y Biomedicina / Biología
description Toll-like receptors (TLRs) play a crucial role in the recognition of pathogen-derived components as a first line of defense against infections. It has been suggested that depending on the nature of the pathogens, TLRs activation induce a distinct cytokine profile that may contribute to the polarization of the acquired immune response. Here, we investigated the early MAPK signaling activation via TLR4 and TLR2 receptors and its impact in differential cytokine profile by macrophages. We found that TLR2 ligands activated MAPKs p38 and ERK earlier compared to the TLR4 ligand LPS in macrophages. Higher IL-10/IL-12 and IL-10/TNF-α ratios were also observed at later time points in response to TLR2 ligands compared to LPS. The results also indicate an earlier activation of the phosphatase MKP-1 and that MKP-1 KO macrophages show a prolongation in p38 phosphorylation in response to TLR2 stimulation. Furthermore, p38 is critical for IL-10 expression in response to TLR2 ligands, which triggers the macrophage change to a M2 and regulatory phenotype in contrast to the M1 phenotype induced by TLR4 activation. Therefore, the early TLR2-mediated p38 induction contributes for the high IL-10 production, likely as a virulence strategy to suppress host Th1 response against certain types of pathogens
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-06-21
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/716826
https://dx.doi.org/10.3389/fimmu.2021.660065
url http://hdl.handle.net/10486/716826
https://dx.doi.org/10.3389/fimmu.2021.660065
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/msword
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A
publisher.none.fl_str_mv Frontiers Media S.A
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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