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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.660065/full |
| _version_ | 1819098556782346240 |
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| author | Sara Francisco Sara Francisco Sara Francisco Alicia Arranz Javier Merino Javier Merino Javier Merino Carmen Punzón Carmen Punzón Rosario Perona Manuel Fresno Manuel Fresno Manuel Fresno |
| author_facet | Sara Francisco Sara Francisco Sara Francisco Alicia Arranz Javier Merino Javier Merino Javier Merino Carmen Punzón Carmen Punzón Rosario Perona Manuel Fresno Manuel Fresno Manuel Fresno |
| author_sort | Sara Francisco |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T00:32:52Z |
| format | Article |
| id | doaj.art-2bf40a59ba9a43eaba3fc44fe71de666 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T00:32:52Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2bf40a59ba9a43eaba3fc44fe71de6662022-12-21T18:44:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.660065660065Early p38 Activation Regulated by MKP-1 Is Determinant for High Levels of IL-10 Expression Through TLR2 ActivationSara Francisco0Sara Francisco1Sara Francisco2Alicia Arranz3Javier Merino4Javier Merino5Javier Merino6Carmen Punzón7Carmen Punzón8Rosario Perona9Manuel Fresno10Manuel Fresno11Manuel Fresno12DIOMUNE S. L., Parque Científico de Madrid, Madrid, SpainCentro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid, SpainCentro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Cientificas (CSIC)-Universidad Autónoma de Madrid, Madrid, SpainCentro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Cientificas (CSIC)-Universidad Autónoma de Madrid, Madrid, SpainDIOMUNE S. L., Parque Científico de Madrid, Madrid, SpainCentro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid, SpainCentro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Cientificas (CSIC)-Universidad Autónoma de Madrid, Madrid, SpainDIOMUNE S. L., Parque Científico de Madrid, Madrid, SpainCentro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid, SpainInstituto de Investigaciones Biomedicas, Alberto Sols Universidad Autónoma de Madrid, Madrid, SpainDIOMUNE S. L., Parque Científico de Madrid, Madrid, SpainCentro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid, SpainCentro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Cientificas (CSIC)-Universidad Autónoma de Madrid, Madrid, SpainToll-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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.660065/fullmacrophagesinnate immunitytoll-like receptorsMAPK signalingcytokines |
| spellingShingle | Sara Francisco Sara Francisco Sara Francisco Alicia Arranz Javier Merino Javier Merino Javier Merino Carmen Punzón Carmen Punzón Rosario Perona Manuel Fresno Manuel Fresno Manuel Fresno Early p38 Activation Regulated by MKP-1 Is Determinant for High Levels of IL-10 Expression Through TLR2 Activation Frontiers in Immunology macrophages innate immunity toll-like receptors MAPK signaling cytokines |
| 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 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.660065/full |
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