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

Stefan Bauer(Institute of Medical Microbiology and Hygiene), Carsten J. Kirschning(Institute of Medical Microbiology and Hygiene), Hans Häcker(Institute of Medical Microbiology and Hygiene), Vanessa Redecke(Institute of Medical Microbiology and Hygiene), Susanne Hausmann(Institute of Medical Microbiology and Hygiene), Shizuo Akira(Institute of Medical Microbiology and Hygiene), Hermann Wagner(Institute of Medical Microbiology and Hygiene), Grayson B. Lipford(Institute of Medical Microbiology and Hygiene)
Proceedings of the National Academy of Sciences
July 24, 2001
10.1073/pnas.161293498
Cited by 1,534Open Access
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Abstract

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.

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