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

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  • Stefan Bauer
    Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
  • Carsten J. Kirschning
    Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
  • Hans Häcker
    Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
  • Vanessa Redecke
    Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
  • Susanne Hausmann
    Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
  • Shizuo Akira
    Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
  • Hermann Wagner
    Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
  • Grayson B. Lipford
    Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan

説明

<jats:p>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.</jats:p>

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