Fasciola gigantica excretory-secretory products (FgESPs) modulate the differentiation and immune functions of buffalo dendritic cells through a mechanism involving DNMT1 and TET1
| العنوان: | Fasciola gigantica excretory-secretory products (FgESPs) modulate the differentiation and immune functions of buffalo dendritic cells through a mechanism involving DNMT1 and TET1 |
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| المؤلفون: | Yaoyao Zhang, Wei Shi, Weiyi Huang, Wen-Ping Zhao, Dongying Wang, Xue-Fang Mei, Zhao-An Sheng, Hong-Lin Luo, Xing-Quan Zhu, Yu-Rui Wang |
| المصدر: | Parasites & Vectors Parasites & Vectors, Vol 13, Iss 1, Pp 1-15 (2020) |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | DNA (Cytosine-5-)-Methyltransferase 1, 0301 basic medicine, Buffaloes, medicine.medical_treatment, Fasciola gigantica, chemical and pharmacologic phenomena, Biology, T-Lymphocytes, Regulatory, lcsh:Infectious and parasitic diseases, Dioxygenases, Host-Parasite Interactions, 03 medical and health sciences, Th2 Cells, 0302 clinical medicine, Immune system, Excretory/secretory products, Histone methylation, medicine, Animals, lcsh:RC109-216, Immune Evasion, Gene knockdown, Research, hemic and immune systems, Cell Differentiation, Dendritic Cells, Helminth Proteins, Methylation, DNA Methylation, Mixed lymphocyte reaction, Interleukin-12, Fasciola, In vitro, Immune functions, Cell biology, 030104 developmental biology, Infectious Diseases, Cytokine, Caspases, Differentiation, DNA methylation, Cytokines, Parasitology, Signal Transduction, 030215 immunology |
| الوصف: | Background Fasciola gigantica infection threatens the health of both humans and animals in the world. The excretory/secretory products (ESPs) of this fluke has been reported to impair the activation and maturation of immune cells. We have previously shown the influence of F. gigantica ESPs (FgESPs) on the maturation of buffalo dendritic cells (DCs). However, the underlying mechanisms remain unclear. The objective of this study was to investigate the potency of FgESPs in shifting the differentiation and immune functions of buffalo DCs. Methods Buffalo DCs were incubated with FgESPs directly or further co-cultured with lymphocytes in vitro. qRT-PCR was employed to determine the gene expression profile of DCs or the mixed cells, and an ELISA was used to measure cytokine levels in the supernatants. Hoechst and Giemsa staining assays, transmission electron microscopy, caspase-3/7 activity test and histone methylation test were performed to determine DC phenotyping, apoptosis and methylation. To investigate the mechanism involved with DNA methylation, a Co-IP assay and immunofluorescent staining assay were performed to observe if there was any direct interaction between FgESPs and DNMT1/TET1 in buffalo DCs, while RNAi technology was employed to knockdown DNMT1 and TET1 in order to evaluate any different influence of FgESPs on DCs when these genes were absent. Results qRT-PCR and ELISA data together demonstrated the upregulation of DC2 and Th2/Treg markers in DCs alone and DCs with a mixed lymphocyte reaction (MLR), suggesting a bias of DC2 that potentially directed Th2 differentiation in vitro. DC apoptosis was also found and evidenced morphologically and biochemically, which might be a source of tolerogenic DCs that led to Treg differentiation. In addition, FgESPs induced methylation level changes of histones H3K4 and H3K9, which correlate with DNA methylation. Co-IP and immunofluorescent subcellular localization assays showed no direct interaction between the FgESPs and DNMT1/TET1 in buffalo DCs. The productions of IL-6 and IL-12 were found separately altered by the knockdown of DNMT1 and TET1 in DCs after FgESPs treatment. Conclusions FgESPs may induce the DC2 phenotype or the apoptosis of buffalo DCs to induce the downstream Th2/Treg response of T cells, possibly through a DNMT1- or TET1-dependent manner(s). |
| تدمد: | 1756-3305 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f1e377343aa9cb37461faff59435acce https://doi.org/10.1186/s13071-020-04220-0 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f1e377343aa9cb37461faff59435acce |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17563305 |
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