Dokument: Beauvericin Targets Toll Like Receptor 4 and Cathepsin B to Promote Dendritic Cell Activation
| Titel: | Beauvericin Targets Toll Like Receptor 4 and Cathepsin B to Promote Dendritic Cell Activation | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=66023 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250616-090751-0 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Yang, Xiaoli [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Scheu, Stefanie [Gutachter] Prof. Dr. Kurz, Thomas [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | BEA, a mycotoxin of the enniatin family produced by various toxigenic fungi, has been attributed multiple biological activities such as anti-cancer, anti-inflammatory, and anti-microbial functions. However, effects of BEA on DCs remain unknown so far. Here, we identified effects of BEA on murine granulocyte–macrophage colony-stimulating factor (GM-CSF)-cultured bone marrow derived dendritic cells (BMDCs) and the underlying molecular mechanisms. BEA potently activates BMDCs as signified by elevated IL-12 and CD86 expression. Multiplex immunoassays performed on myeloid differentiation primary response 88 (MyD88) and toll/interleukin-1 receptor (TIR) domain containing adaptor inducing interferon beta (TRIF) single or double deficient BMDCs indicate that BEA induces inflammatory cytokine and chemokine production in a MyD88/TRIF dependent manner. Furthermore, we found that BEA was not able to induce IL-12 or IFNβ production in Toll-like receptor 4 (Tlr4)-deficient BMDCs, whereas induction of these cytokines was not compromised in Tlr3/7/9-deficient BMDCs. This suggests that TLR4 might be the functional target of BEA on BMDCs. Consistently, in luciferase reporter assays BEA stimulation significantly promotes NF-κB activation in mTLR4/CD14/MD2 overexpressing but not control HEK-293 cells. RNA-sequencing analyses further confirmed that BEA induces transcriptional changes associated with the TLR4 signaling pathway.
In addition, by using an online in silico prediction tool, CTSB was predicted to be a target of BEA. This was confirmed by CTSB cell-based assays within human and mouse DCs. CTSB cell-free experiments further indicated that BEA can directly target human and mouse CTSB. Together, these results identify TLR4 as a cellular BEA sensor and define BEA as a potent activator of BMDCs. Moreover, CTSB was identified as another direct target of BEA. These results imply that this compound can be exploited as a promising candidate structure for vaccine adjuvants or cancer immunotherapies. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät » Institute » Institut für Medizinische Mikrobiologie | |||||||
| Dokument erstellt am: | 16.06.2025 | |||||||
| Dateien geändert am: | 16.06.2025 | |||||||
| Promotionsantrag am: | 30.01.2024 | |||||||
| Datum der Promotion: | 17.05.2024 |
