Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation
Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation
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DOI：
10.4049/jimmunol.171.3.1393
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发表时间：
2003-08-01
影响因子：
4.4
通讯作者：
Klinman, DM
中科院分区：
文献类型：
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作者：
Gursel, I;Gursel, M;Klinman, DM
细菌DNA含有免疫刺激性CpG基序，其触发能够在感染性攻击后促进宿主存活的先天免疫应答。然而，CpG驱动的免疫激活也可能产生有害的后果，从自身免疫病到死亡。我们发现，在哺乳动物端粒中，但在细菌中罕见的高频率存在的重复元件，下调CpG诱导的免疫激活。抑制活性与端粒TTAGGG重复形成G-四联体的能力相关。CpG DNA与Toll样受体9在内体囊泡中的共定位被这些重复元件破坏，尽管细胞结合和摄取保持不变。这些发现首次确定了特异性宿主衍生分子可以下调TLR配体引起的先天免疫应答。
Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoinumme disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-tetrads. Colocalization of CpG DNA with Toll-like receptor 9 in endosomal vesicles is disrupted by these repetitive elements, although cellular binding and uptake remain unchanged. These findings are the first to establish that specific host-derived molecules can down-regulate the innate immune response elicited by a TLR ligand.