PDF(Pubmed)
Abstract：
Increasing evidence confirms that histone modification plays a critical role in preserving long-term immunological memory. Immune priming is a novel form of immunological memory recently verified in invertebrates. Toll-like receptor (TLR) signaling and cytokines have been reported to be involved in the immune priming of the Pacific oyster Crassostrea gigas. In the present study, the expression of Toll-like receptor 3 (CgTLR3), myeloid differentiation factor 88-2 (CgMyd88-2) and interleukin 17-1 (CgIL17-1) was found to be elevated in the hemocytes of C. gigas at 6 h after the secondary stimulation with Vibrio splendidus, which was significantly higher than that at 6 h after the primary stimulation (p < 0.05). A significant increase in histone H3 lysine 4 trimethylation (H3K4me3) enrichment was detected in the promoter region of the CgTLR3 gene at 7 d after the primary stimulation with inactivated V. splendidus (p < 0.05). After the treatment with a histone methyltransferase inhibitor (5\'-methylthioadenosine, MTA), the level of H3K4me3 at the promoter of the CgTLR3 gene decreased significantly at 7 d after the primary stimulation with inactivated V. splendidus (p < 0.05), and the expression of CgTLR3, CgMyD88-2 and CgIL17-1 was significantly repressed at 6 h after the secondary stimulation with V. splendidus (p < 0.05). Conversely, the treatment with monomethyl fumarate (MEF, an inhibitor of histone demethylases) resulted in a significant increase in H3K4me3 enrichment levels at the CgTLR3 promoter at 7 d after the primary stimulation (p < 0.05), and the expression of CgTLR3, CgMyD88-2 and CgIL17-1 was observed to increase significantly at 6 h after the secondary stimulation (p < 0.05). These results suggested that H3K4me3 regulated MyD88-dependent TLR signaling in the hemocytes of C. gigas, which defined the role of histone modifications in invertebrate immune priming.
摘要：
越来越多的证据证实，组蛋白修饰在保持长期免疫记忆中起着关键作用。免疫启动是最近在无脊椎动物中验证的一种新形式的免疫记忆。据报道，Toll样受体（TLR）信号和细胞因子与太平洋牡蛎Crassostreagigas的免疫引发有关。在本研究中,Toll样受体3（CgTLR3）的表达，发现骨髓分化因子88-2（CgMyd88-2）和白介素17-1（CgIL17-1）在用脾弧菌二次刺激后6小时在C.gigas的血细胞中升高，显著高于初次刺激后6h(p<0.05)。在用灭活的脾弧菌初次刺激后7d，在CgTLR3基因的启动子区域检测到组蛋白H3赖氨酸4三甲基化（H3K4me3）富集显着增加（p<0.05）。在用组蛋白甲基转移酶抑制剂（5'-甲硫腺苷，MTA),CgTLR3基因启动子的H3K4me3水平在用灭活的脾弧菌初次刺激后7d显著降低(p<0.05),CgTLR3，CgMyD88-2和CgIL17-1的表达在用脾弧菌二次刺激后6h被显着抑制（p<0.05）。相反，用富马酸单甲酯(MEF，组蛋白脱甲基酶的抑制剂）导致在初次刺激后7d，CgTLR3启动子处的H3K4me3富集水平显着增加（p<0.05），在二次刺激后6h，观察到CgTLR3，CgMyD88-2和CgIL17-1的表达显着增加（p<0.05）。这些结果表明，H3K4me3调节了C.gigas血细胞中MyD88依赖性TLR信号传导，其中定义了组蛋白修饰在无脊椎动物免疫引发中的作用。
