Bacterial RNA is recognized by different sets of immunoreceptors
Bacterial RNA is recognized by different sets of immunoreceptors
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DOI：
10.1002/eji.200838978
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发表时间：
2009-09-01
影响因子：
5.4
通讯作者：
Dalpke, Alexander H.
中科院分区：
文献类型：
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作者：
Eberle, Florian;Sirin, Mehtap;Dalpke, Alexander H.
先天免疫通过内体 TLR 和胞质识别系统识别微生物核酸。尽管人们对病毒 RNA 和细菌 DNA 的核酸识别特性的了解不断增加，但对原核 RNA 的免疫原性知之甚少。在这里，我们证明细菌 RNA 是人类 PBMC 中 I 型 IFN 分泌的有效触发因素。人浆细胞样树突状细胞的激活依赖于内体成熟，并且可以被 TLR7 特异性抑制剂阻断。来自TLR7缺陷小鼠的浆细胞样树突状细胞对细菌RNA没有反应。令人惊讶的是，在骨髓 DC 中，TLR 对于细菌 RNA 诱导的 TNF-α 和 IL-12 来说是可有可无的。即使非免疫基质细胞也能够在细菌 RNA 触发后产生 NF-κ B 反应。可以排除视黄酸诱导基因 I 和黑色素瘤分化相关基因 5 与这种反应有关。尽管炎性体衔接蛋白、凋亡相关斑点样蛋白和功能性 I 型 IFN 受体对于髓样 DC 中 IL-1 β 的分泌是必需的，但这些蛋白对于胞质细菌 RNA 诱导 TNF-α 和 IL-1 来说是可有可无的。我们的结果表明，除了激活 TLR7 和炎症小体之外，细菌 RNA 还激活其他胞质受体，与已报道的细菌 DNA 识别类似。
Innate immunity recognizes microbial nucleic acids by endosomal TLR and cytosolic recognition systems. Despite increasing knowledge on the properties of nucleic acid recognition for viral RNA and bacterial DNA, little is known about the immunogenicity of prokaryotic RNA. Here we show that bacterial RNA is a potent trigger for type-I IFN secretion in human PBMC. Activation of human plasmacytoid dendritic cells was dependent on endosomal maturation and could be blocked by a TLR7-specific inhibitor. Murine plasmacytoid dendritic cells from TLR7-deficient mice were unresponsive to bacterial RNA. Surprisingly, in myeloid DC, TLR were dispensable for TNF-alpha and IL-12 induction by bacterial RNA. Even non-immune stroma cells were able to mount a NF-kappa B response upon triggering with bacterial RNA. Retinoic-acid inducible gene I and melanoma-differentiation-associated gene 5 could be ruled out to be responsible for this reactivity. Although the inflammasome adaptor protein, apoptosis-associated speck-like protein, and a functional type-I IFN receptor were necessary for IL-1 beta secretion in myeloid DC, these proteins were dispensable for TNF-alpha and IL-1 induction by cytosolic bacterial RNA. Our results show that besides of activation of TLR7 and inflammasomes, bacterial RNA activates additional cytosolic receptors similarly as has been reported for recognition of bacterial DNA.