3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors
Abstract In the gut ecosystem, microorganisms regulate group behaviour and interplay with the host via a molecular system called quorum sensing (QS). The QS molecule 3-oxo-C12:2-HSL, first identified in human gut microbiota, exerts anti-inflammatory effects and could play a role in inflammatory bowe...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13451-3 |
| _version_ | 1828796817231314944 |
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| author | Garance Coquant Doriane Aguanno Loïc Brot Christine Belloir Julie Delugeard Nathalie Roger Hang-Phuong Pham Loïc Briand Marielle Moreau Luisa de Sordi Véronique Carrière Jean-Pierre Grill Sophie Thenet Philippe Seksik |
| author_facet | Garance Coquant Doriane Aguanno Loïc Brot Christine Belloir Julie Delugeard Nathalie Roger Hang-Phuong Pham Loïc Briand Marielle Moreau Luisa de Sordi Véronique Carrière Jean-Pierre Grill Sophie Thenet Philippe Seksik |
| author_sort | Garance Coquant |
| collection | DOAJ |
| description | Abstract In the gut ecosystem, microorganisms regulate group behaviour and interplay with the host via a molecular system called quorum sensing (QS). The QS molecule 3-oxo-C12:2-HSL, first identified in human gut microbiota, exerts anti-inflammatory effects and could play a role in inflammatory bowel diseases where dysbiosis has been described. Our aim was to identify which signalling pathways are involved in this effect. We observed that 3-oxo-C12:2-HSL decreases expression of pro-inflammatory cytokines such as Interleukine-1β (− 35%) and Tumor Necrosis Factor-α (TNFα) (− 40%) by stimulated immune RAW264.7 cells and decreased TNF secretion by stimulated PBMC in a dose-dependent manner, between 25 to 100 µM. Transcriptomic analysis of RAW264.7 cells exposed to 3-oxo-C12:2-HSL, in a pro-inflammatory context, highlighted JAK-STAT, NF-κB and TFN signalling pathways and we confirmed that 3-oxo-C12:2-HSL inhibited JAK1 and STAT1 phosphorylation. We also showed through a screening assay that 3-oxo-C12:2-HSL interacted with several human bitter taste receptors. Its anti-inflammatory effect involved TAS2R38 as shown by pharmacologic inhibition and led to an increase in intracellular calcium levels. We thus unravelled the involvement of several cellular pathways in the anti-inflammatory effects exerted by the QS molecule 3-oxo-C12:2-HSL. |
| first_indexed | 2024-12-12T04:29:35Z |
| format | Article |
| id | doaj.art-b8792f0195a14d089cac4c1d13deb817 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T04:29:35Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b8792f0195a14d089cac4c1d13deb8172022-12-22T00:38:08ZengNature PortfolioScientific Reports2045-23222022-06-0112111310.1038/s41598-022-13451-33-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptorsGarance Coquant0Doriane Aguanno1Loïc Brot2Christine Belloir3Julie Delugeard4Nathalie Roger5Hang-Phuong Pham6Loïc Briand7Marielle Moreau8Luisa de Sordi9Véronique Carrière10Jean-Pierre Grill11Sophie Thenet12Philippe Seksik13Sorbonne Université, INSERM, Centre de Recherche Saint-AntoineSorbonne Université, INSERM, Centre de Recherche Saint-AntoineSorbonne Université, INSERM, Centre de Recherche Saint-AntoineCentre des Sciences du Goût et de l’Alimentation, UMR 1324 INRAE, UMR 6265 CNRS, University of Bourgogne Franche-ComtéSorbonne Université, INSERM, Centre de Recherche Saint-AntoineSorbonne Université, INSERM, Centre de Recherche Saint-AntoineParean BiotechnologiesCentre des Sciences du Goût et de l’Alimentation, UMR 1324 INRAE, UMR 6265 CNRS, University of Bourgogne Franche-ComtéLVMH Recherche, Life Science DepartmentSorbonne Université, INSERM, Centre de Recherche Saint-AntoineSorbonne Université, INSERM, Centre de Recherche Saint-AntoineSorbonne Université, INSERM, Centre de Recherche Saint-AntoineSorbonne Université, INSERM, Centre de Recherche Saint-AntoineSorbonne Université, INSERM, Centre de Recherche Saint-AntoineAbstract In the gut ecosystem, microorganisms regulate group behaviour and interplay with the host via a molecular system called quorum sensing (QS). The QS molecule 3-oxo-C12:2-HSL, first identified in human gut microbiota, exerts anti-inflammatory effects and could play a role in inflammatory bowel diseases where dysbiosis has been described. Our aim was to identify which signalling pathways are involved in this effect. We observed that 3-oxo-C12:2-HSL decreases expression of pro-inflammatory cytokines such as Interleukine-1β (− 35%) and Tumor Necrosis Factor-α (TNFα) (− 40%) by stimulated immune RAW264.7 cells and decreased TNF secretion by stimulated PBMC in a dose-dependent manner, between 25 to 100 µM. Transcriptomic analysis of RAW264.7 cells exposed to 3-oxo-C12:2-HSL, in a pro-inflammatory context, highlighted JAK-STAT, NF-κB and TFN signalling pathways and we confirmed that 3-oxo-C12:2-HSL inhibited JAK1 and STAT1 phosphorylation. We also showed through a screening assay that 3-oxo-C12:2-HSL interacted with several human bitter taste receptors. Its anti-inflammatory effect involved TAS2R38 as shown by pharmacologic inhibition and led to an increase in intracellular calcium levels. We thus unravelled the involvement of several cellular pathways in the anti-inflammatory effects exerted by the QS molecule 3-oxo-C12:2-HSL.https://doi.org/10.1038/s41598-022-13451-3 |
| spellingShingle | Garance Coquant Doriane Aguanno Loïc Brot Christine Belloir Julie Delugeard Nathalie Roger Hang-Phuong Pham Loïc Briand Marielle Moreau Luisa de Sordi Véronique Carrière Jean-Pierre Grill Sophie Thenet Philippe Seksik 3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors Scientific Reports |
| title | 3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors |
| title_full | 3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors |
| title_fullStr | 3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors |
| title_full_unstemmed | 3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors |
| title_short | 3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors |
| title_sort | 3 oxo c12 2 hsl quorum sensing molecule from human intestinal microbiota inhibits pro inflammatory pathways in immune cells via bitter taste receptors |
| url | https://doi.org/10.1038/s41598-022-13451-3 |
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