2. Academic Validation
  3. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition

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

  • Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9237-42. doi: 10.1073/pnas.161293498.
S Bauer 1,  C J Kirschning,  H Häcker,  V Redecke,  S Hausmann,  S Akira,  H Wagner,  G B Lipford
Affiliations

Affiliation

  • 1 Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany. [email protected]
PMID: 11470918 DOI: 10.1073/pnas.161293498
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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