人类Toll样受体9通过物种特异性的CpG基序识别赋予对细菌DNA的反应性。
Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition.
作者信息
Bauer S, Kirschning C J, Häcker H, Redecke V, Hausmann S, Akira S, Wagner H, Lipford G B
机构信息
Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany.
出版信息
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9237-42. doi: 10.1073/pnas.161293498. Epub 2001 Jul 24.
The Toll-like receptor (TLR) family consists of phylogenetically conserved transmembrane proteins, which function as mediators of innate immunity for recognition of pathogen-derived ligands and subsequent cell activation via the Toll/IL-1R signal pathway. Here, we show that human TLR9 (hTLR9) expression in human immune cells correlates with responsiveness to bacterial deoxycytidylate-phosphate-deoxyguanylate (CpG)-DNA. Notably "gain of function" to immunostimulatory CpG-DNA is achieved by expressing TLR9 in human nonresponder cells. Transfection of either human or murine TLR9 conferred responsiveness in a CD14- and MD2-independent manner, yet required species-specific CpG-DNA motifs for initiation of the Toll/IL-1R signal pathway via MyD88. The optimal CpG motif for hTLR9 was GTCGTT, whereas the optimal murine sequence was GACGTT. Overall, these data suggest that hTLR9 conveys CpG-DNA responsiveness to human cells by directly engaging immunostimulating CpG-DNA.
Toll样受体（TLR）家族由系统发育保守的跨膜蛋白组成，这些蛋白作为天然免疫的介质，用于识别病原体衍生的配体，并通过Toll/IL-1R信号通路随后激活细胞。在此，我们表明人类免疫细胞中人类TLR9（hTLR9）的表达与对细菌脱氧胞苷酸-磷酸-脱氧鸟苷酸（CpG）-DNA的反应性相关。值得注意的是，通过在人类无反应细胞中表达TLR9可实现对免疫刺激CpG-DNA的“功能获得”。转染人类或小鼠TLR9均以不依赖CD14和MD2的方式赋予反应性，但需要物种特异性的CpG-DNA基序通过MyD88启动Toll/IL-1R信号通路。hTLR9的最佳CpG基序是GTCGTT，而最佳小鼠序列是GACGTT。总体而言，这些数据表明hTLR9通过直接结合免疫刺激CpG-DNA将CpG-DNA反应性传递给人类细胞。
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