التفاصيل البيبلوغرافية
العنوان: |
The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells via Activating the TLR4 Signaling Pathway |
المؤلفون: |
Yang, Xiaoli, Ali, Shafaqat, Zhao, Manman, Richter, Lisa, Schäfer, Vanessa, Schliehe-Diecks, Julian, Frank, Marian, Qi, Jing, Larsen, Pia-Katharina, Skerra, Jennifer, Islam, Heba, Wachtmeister, Thorsten, Alter, Christina, Huang, Anfei, Bhatia, Sanil, Köhrer, Karl, Kirschning, Carsten, Weighardt, Heike, Kalinke, Ulrich, Kalscheuer, Rainer, Uhrberg, Markus, Scheu, Stefanie |
المساهمون: |
Deutsche Forschungsgemeinschaft |
المصدر: |
Frontiers in Immunology ; volume 13 ; ISSN 1664-3224 |
بيانات النشر: |
Frontiers Media SA |
سنة النشر: |
2022 |
المجموعة: |
Frontiers (Publisher - via CrossRef) |
مصطلحات موضوعية: |
Immunology, Immunology and Allergy |
الوصف: |
Beauvericin (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 dendritic cells 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. Together, these results identify TLR4 as a cellular BEA sensor and define BEA as a potent activator of BMDCs, implying that this compound can be exploited as a promising candidate structure for vaccine adjuvants or cancer immunotherapies. |
نوع الوثيقة: |
article in journal/newspaper |
اللغة: |
unknown |
DOI: |
10.3389/fimmu.2022.856230 |
DOI: |
10.3389/fimmu.2022.856230/full |
الإتاحة: |
https://doi.org/10.3389/fimmu.2022.856230Test |
حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
رقم الانضمام: |
edsbas.BD39172C |
قاعدة البيانات: |
BASE |