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

被引：1254

作者：

Bauer, S ^{[1
]}

Kirschning, CJ

Häcker, H

Redecke, V

Hausmann, S

Akira, S

Wagner, H

Lipford, GB

机构：

[1] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany

[2] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2001年 / 98卷 / 16期

关键词：

D O I：

10.1073/pnas.161293498

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 deoxy-cytidylate-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.

引用

页码：9237 / 9242

页数：6

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