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PMID: 11470918 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 16 ·2001-07-31 ·Pages 9237-42

Bauer S, Kirschning CJ, Häcker H, Redecke V, Hausmann S, Akira S, Wagner H, Lipford GB

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.

MeSH Terms
Animals Base Sequence Cell Line CpG Islands DNA Primers DNA, Bacterial/immunology DNA, Complementary DNA-Binding Proteins/genetics,immunology Genetic Complementation Test Humans Mice Molecular Sequence Data Receptors, Cell Surface/genetics,immunology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Species Specificity Toll-Like Receptor 9
Chemicals
DNA Primers DNA, Bacterial DNA, Complementary DNA-Binding Proteins Receptors, Cell Surface TLR9 protein, human Tlr9 protein, mouse Toll-Like Receptor 9
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bauer S
Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany. stefan.bauer@lrz.tum.de
Kirschning C J
Häcker H
Redecke V
Hausmann S
Akira S
Wagner H
Lipford G B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.161293498
Email
stefan.bauer@lrz.tum.de
Published
2001-07-31
Epub
2001-00-24
Pages
9237-42
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC55404
Subset
IM
Databases
GENBANK
AF348140
External Links
PubMed source DOI: 10.1073/pnas.161293498 PMC Full Text View journal details
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