Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition

作者：Stefan Bauer, Carsten J. Kirschning, Hans Häcker, Vanessa Redecke, Susanne Hausmann, Shizuo Akira, Hermann Wagner, Grayson B. Lipford · 发表于：Proceedings of the National Academy of Sciences · 年份：2001 · DOI：10.1073/pnas.161293498 · 被引用次数：1545 · 研究领域：Immune Response and Inflammation、Immune Cell Function and Interaction、Antimicrobial Peptides and Activities

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.