Coactivation of TLR2 and TLR8 in Primary Human Monocytes Triggers a Distinct Inflammatory Signaling Response
Innate immune signaling is essential to mount a fast and specific immune response to pathogens. Monocytes and macrophages are essential cells in the early response in their capacity as ubiquitous phagocytic cells. They phagocytose microorganisms or damaged cells and sense pathogen/damage-associated...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.00618/full |
| _version_ | 1818407263660933120 |
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| author | Korbinian Bösl Miriam Giambelluca Markus Haug Markus Haug Marit Bugge Terje Espevik Richard K. Kandasamy Richard K. Kandasamy Bjarte Bergstrøm Bjarte Bergstrøm |
| author_facet | Korbinian Bösl Miriam Giambelluca Markus Haug Markus Haug Marit Bugge Terje Espevik Richard K. Kandasamy Richard K. Kandasamy Bjarte Bergstrøm Bjarte Bergstrøm |
| author_sort | Korbinian Bösl |
| collection | DOAJ |
| description | Innate immune signaling is essential to mount a fast and specific immune response to pathogens. Monocytes and macrophages are essential cells in the early response in their capacity as ubiquitous phagocytic cells. They phagocytose microorganisms or damaged cells and sense pathogen/damage-associated molecular patterns (PAMPs/DAMPs) through innate receptors such as Toll-like receptors (TLRs). We investigated a phenomenon where co-signaling from TLR2 and TLR8 in human primary monocytes provides a distinct immune activation profile compared to signaling from either TLR alone. We compare gene signatures induced by either stimulus alone or together and show that co-signaling results in downstream differences in regulation of signaling and gene transcription. We demonstrate that these differences result in altered cytokine profiles between single and multi-receptor signaling, and show how it can influence both T-cell and neutrophil responses. The end response is tailored to combat extracellular pathogens, possibly by modifying the regulation of IFNβ and IL12-family cytokines. |
| first_indexed | 2024-12-14T09:25:04Z |
| format | Article |
| id | doaj.art-1f5e66cebcf545df8cbf53d5e4dc88ce |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-14T09:25:04Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-1f5e66cebcf545df8cbf53d5e4dc88ce2022-12-21T23:08:13ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-05-01910.3389/fphys.2018.00618331723Coactivation of TLR2 and TLR8 in Primary Human Monocytes Triggers a Distinct Inflammatory Signaling ResponseKorbinian Bösl0Miriam Giambelluca1Markus Haug2Markus Haug3Marit Bugge4Terje Espevik5Richard K. Kandasamy6Richard K. Kandasamy7Bjarte Bergstrøm8Bjarte Bergstrøm9Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Infection, St. Olav’s University Hospital, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Infection, St. Olav’s University Hospital, Trondheim, NorwayInnate immune signaling is essential to mount a fast and specific immune response to pathogens. Monocytes and macrophages are essential cells in the early response in their capacity as ubiquitous phagocytic cells. They phagocytose microorganisms or damaged cells and sense pathogen/damage-associated molecular patterns (PAMPs/DAMPs) through innate receptors such as Toll-like receptors (TLRs). We investigated a phenomenon where co-signaling from TLR2 and TLR8 in human primary monocytes provides a distinct immune activation profile compared to signaling from either TLR alone. We compare gene signatures induced by either stimulus alone or together and show that co-signaling results in downstream differences in regulation of signaling and gene transcription. We demonstrate that these differences result in altered cytokine profiles between single and multi-receptor signaling, and show how it can influence both T-cell and neutrophil responses. The end response is tailored to combat extracellular pathogens, possibly by modifying the regulation of IFNβ and IL12-family cytokines.https://www.frontiersin.org/article/10.3389/fphys.2018.00618/fullinnate immunityToll-like receptorsToll-like receptor 2Toll-like receptor 8signalingmonocytes |
| spellingShingle | Korbinian Bösl Miriam Giambelluca Markus Haug Markus Haug Marit Bugge Terje Espevik Richard K. Kandasamy Richard K. Kandasamy Bjarte Bergstrøm Bjarte Bergstrøm Coactivation of TLR2 and TLR8 in Primary Human Monocytes Triggers a Distinct Inflammatory Signaling Response Frontiers in Physiology innate immunity Toll-like receptors Toll-like receptor 2 Toll-like receptor 8 signaling monocytes |
| title | Coactivation of TLR2 and TLR8 in Primary Human Monocytes Triggers a Distinct Inflammatory Signaling Response |
| title_full | Coactivation of TLR2 and TLR8 in Primary Human Monocytes Triggers a Distinct Inflammatory Signaling Response |
| title_fullStr | Coactivation of TLR2 and TLR8 in Primary Human Monocytes Triggers a Distinct Inflammatory Signaling Response |
| title_full_unstemmed | Coactivation of TLR2 and TLR8 in Primary Human Monocytes Triggers a Distinct Inflammatory Signaling Response |
| title_short | Coactivation of TLR2 and TLR8 in Primary Human Monocytes Triggers a Distinct Inflammatory Signaling Response |
| title_sort | coactivation of tlr2 and tlr8 in primary human monocytes triggers a distinct inflammatory signaling response |
| topic | innate immunity Toll-like receptors Toll-like receptor 2 Toll-like receptor 8 signaling monocytes |
| url | https://www.frontiersin.org/article/10.3389/fphys.2018.00618/full |
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