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. Epub 2001 Jul 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • CpG Islands*
  • DNA Primers
  • DNA, Bacterial / immunology*
  • DNA, Complementary
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Genetic Complementation Test
  • Humans
  • Mice
  • Molecular Sequence Data
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Species Specificity
  • Toll-Like Receptor 9

Substances

  • DNA Primers
  • DNA, Bacterial
  • DNA, Complementary
  • DNA-Binding Proteins
  • Receptors, Cell Surface
  • TLR9 protein, human
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9

Associated data

  • GENBANK/AF348140