Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition.
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.
Bauer
S
S
Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany. stefan.bauer@lrz.tum.de
Kirschning
C J
CJ
Häcker
H
H
Redecke
V
V
Hausmann
S
S
Akira
S
S
Wagner
H
H
Lipford
G B
GB
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018899:CpG Islands; D017931:DNA Primers; D004269:DNA, Bacterial / Q000276:immunology*; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005816:Genetic Complementation Test; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013045:Species Specificity; D051217:Toll-Like Receptor 9
D017931:DNA Primers; D004269:DNA, Bacterial; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9