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...
| Authors: | ; ; ; ; ; |
|---|---|
| Format: | Article |
| Publication date: | 2021 |
| Country: | España |
| Institution: | Universidad Autónoma de Madrid |
| Repository: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Language: | English |
| OAI Identifier: | oai:repositorio.uam.es:10486/716826 |
| Online Access: | http://hdl.handle.net/10486/716826 https://dx.doi.org/10.3389/fimmu.2021.660065 |
| Access Level: | Open access |
| Keyword: | Macrophages innate immunity toll-like receptors MAPK signaling cytokines Biología y Biomedicina / Biología |
| _version_ | 1878732044184322048 |
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| author | Francisco, Sara |
| author2 | Arranz, Alicia Merino, Javier Punzón, Carmen Perona Abellón, Rosario Fresno Escudero, Manuel |
| author2_role | author author author author author |
| author_browse | Arranz, Alicia Francisco, Sara Fresno Escudero, Manuel Merino, Javier Perona Abellón, Rosario Punzón, Carmen |
| author_facet | Francisco, Sara Arranz, Alicia Merino, Javier Punzón, Carmen Perona Abellón, Rosario Fresno Escudero, Manuel |
| author_role | author |
| collection | Biblos-e Archivo. Repositorio Institucional de la UAM |
| 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 |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_3bbfb8263ebde088bf7cdc81e0820ca5 |
| institution | Universidad Autónoma de Madrid |
| instname_str | Universidad Autónoma de Madrid |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repositorio.uam.es:10486/716826 |
| publishDate | 2021 |
| publishDateSort | 2021 |
| publisher | Frontiers Media S.A |
| publisherStr | Frontiers Media S.A |
| reponame_str | Biblos-e Archivo. Repositorio Institucional de la UAM |
| spelling | Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation Francisco, Sara Arranz, Alicia Merino, Javier Punzón, Carmen Perona Abellón, Rosario Fresno Escudero, Manuel Macrophages innate immunity toll-like receptors MAPK signaling cytokines Biología y Biomedicina / Biología 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 This 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.A http://hdl.handle.net/10486/716826 https://dx.doi.org/10.3389/fimmu.2021.660065 |
| 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 | 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_short | 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 |
| topic | Macrophages innate immunity toll-like receptors MAPK signaling cytokines Biología y Biomedicina / Biología |
| topic_facet | Macrophages innate immunity toll-like receptors MAPK signaling cytokines Biología y Biomedicina / Biología |
| url | http://hdl.handle.net/10486/716826 https://dx.doi.org/10.3389/fimmu.2021.660065 |