Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling
Abstract The discovery of Toll-like receptors (TLRs) represented a significant breakthrough that paved the way for the study of host-pathogen interactions in innate immunity. However, there are still major gaps in understanding TLR function, especially regarding the early dynamics of downstream TLR...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53770-9 |
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| _version_ | 1846165032988049408 |
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| author | Janine Holze Felicitas Lauber Sofía Soler Evi Kostenis Günther Weindl |
| author_facet | Janine Holze Felicitas Lauber Sofía Soler Evi Kostenis Günther Weindl |
| author_sort | Janine Holze |
| collection | DOAJ |
| description | Abstract The discovery of Toll-like receptors (TLRs) represented a significant breakthrough that paved the way for the study of host-pathogen interactions in innate immunity. However, there are still major gaps in understanding TLR function, especially regarding the early dynamics of downstream TLR pathways. Here, we present a label-free optical biosensor-based assay as a method for detecting TLR activation in a native and label-free environment and defining the dynamics of TLR pathway activation. This technology is sufficiently sensitive to detect TLR signaling and readily discriminates between different TLR signaling pathways. We define pharmacological modulators of cell surface and endosomal TLRs and downstream signaling molecules and uncover TLR signaling signatures, including potential biased receptor signaling. These findings highlight that optical biosensor assays complement traditional assays that use a single endpoint and have the potential to facilitate the future design of selective drugs targeting TLRs and their downstream effector cascades. |
| format | Article |
| id | doaj-art-37bf9c0a7b764eb09cf33fb88df72697 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-37bf9c0a7b764eb09cf33fb88df726972024-11-17T12:37:07ZengNature PortfolioNature Communications2041-17232024-11-0115111810.1038/s41467-024-53770-9Label-free biosensor assay decodes the dynamics of Toll-like receptor signalingJanine Holze0Felicitas Lauber1Sofía Soler2Evi Kostenis3Günther Weindl4Pharmaceutical Institute, Section Pharmacology and Toxicology, University of BonnPharmaceutical Institute, Section Pharmacology and Toxicology, University of BonnInstitute of Experimental Haematology and Transfusion Medicine, University Hospital BonnInstitute for Pharmaceutical Biology, Molecular, Cellular and Pharmacobiology Section, University of BonnPharmaceutical Institute, Section Pharmacology and Toxicology, University of BonnAbstract The discovery of Toll-like receptors (TLRs) represented a significant breakthrough that paved the way for the study of host-pathogen interactions in innate immunity. However, there are still major gaps in understanding TLR function, especially regarding the early dynamics of downstream TLR pathways. Here, we present a label-free optical biosensor-based assay as a method for detecting TLR activation in a native and label-free environment and defining the dynamics of TLR pathway activation. This technology is sufficiently sensitive to detect TLR signaling and readily discriminates between different TLR signaling pathways. We define pharmacological modulators of cell surface and endosomal TLRs and downstream signaling molecules and uncover TLR signaling signatures, including potential biased receptor signaling. These findings highlight that optical biosensor assays complement traditional assays that use a single endpoint and have the potential to facilitate the future design of selective drugs targeting TLRs and their downstream effector cascades.https://doi.org/10.1038/s41467-024-53770-9 |
| spellingShingle | Janine Holze Felicitas Lauber Sofía Soler Evi Kostenis Günther Weindl Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling Nature Communications |
| title | Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling |
| title_full | Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling |
| title_fullStr | Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling |
| title_full_unstemmed | Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling |
| title_short | Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling |
| title_sort | label free biosensor assay decodes the dynamics of toll like receptor signaling |
| url | https://doi.org/10.1038/s41467-024-53770-9 |
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