Literature DB >> 11470918

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

S Bauer1, C J Kirschning, H Häcker, V Redecke, S Hausmann, S Akira, H Wagner, G B Lipford.   

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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Year:  2001        PMID: 11470918      PMCID: PMC55404          DOI: 10.1073/pnas.161293498

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  44 in total

1.  MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways.

Authors:  R Medzhitov; P Preston-Hurlburt; E Kopp; A Stadlen; C Chen; S Ghosh; C A Janeway
Journal:  Mol Cell       Date:  1998-08       Impact factor: 17.970

2.  Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines.

Authors:  G B Lipford; T Sparwasser; M Bauer; S Zimmermann; E S Koch; K Heeg; H Wagner
Journal:  Eur J Immunol       Date:  1997-12       Impact factor: 5.532

3.  Identification and characterization of an IkappaB kinase.

Authors:  C H Régnier; H Y Song; X Gao; D V Goeddel; Z Cao; M Rothe
Journal:  Cell       Date:  1997-07-25       Impact factor: 41.582

4.  Macrophages sense pathogens via DNA motifs: induction of tumor necrosis factor-alpha-mediated shock.

Authors:  T Sparwasser; T Miethke; G Lipford; A Erdmann; H Häcker; K Heeg; H Wagner
Journal:  Eur J Immunol       Date:  1997-07       Impact factor: 5.532

5.  A family of human receptors structurally related to Drosophila Toll.

Authors:  F L Rock; G Hardiman; J C Timans; R A Kastelein; J F Bazan
Journal:  Proc Natl Acad Sci U S A       Date:  1998-01-20       Impact factor: 11.205

6.  CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation.

Authors:  H Häcker; H Mischak; T Miethke; S Liptay; R Schmid; T Sparwasser; K Heeg; G B Lipford; H Wagner
Journal:  EMBO J       Date:  1998-11-02       Impact factor: 11.598

7.  Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.

Authors:  O Adachi; T Kawai; K Takeda; M Matsumoto; H Tsutsui; M Sakagami; K Nakanishi; S Akira
Journal:  Immunity       Date:  1998-07       Impact factor: 31.745

8.  Identification and characterization of a family of mammalian methyl-CpG binding proteins.

Authors:  B Hendrich; A Bird
Journal:  Mol Cell Biol       Date:  1998-11       Impact factor: 4.272

Review 9.  Oligonucleotide adjuvants for T helper 1 (Th1)-specific vaccination.

Authors:  D A Carson; E Raz
Journal:  J Exp Med       Date:  1997-11-17       Impact factor: 14.307

10.  CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity.

Authors:  R S Chu; O S Targoni; A M Krieg; P V Lehmann; C V Harding
Journal:  J Exp Med       Date:  1997-11-17       Impact factor: 14.307

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  366 in total

Review 1.  Activation of the immune system by bacterial CpG-DNA.

Authors:  Georg Häcker; Vanessa Redecke; Hans Häcker
Journal:  Immunology       Date:  2002-03       Impact factor: 7.397

2.  IVIg attenuates TLR-9 activation in B cells from SLE patients.

Authors:  Aharon Kessel; Regina Peri; Tharwat Haj; Ayelet Snir; Gleb Slobodin; Edmond Sabo; Itzhak Rosner; Yehuda Shoenfeld; Elias Toubi
Journal:  J Clin Immunol       Date:  2010-10-05       Impact factor: 8.317

3.  Metabolic biotinylation of recombinant proteins in mammalian cells and in mice.

Authors:  M B Parrott; M A Barry
Journal:  Mol Ther       Date:  2000-01       Impact factor: 11.454

4.  New approaches to sepsis: molecular diagnostics and biomarkers.

Authors:  Konrad Reinhart; Michael Bauer; Niels C Riedemann; Christiane S Hartog
Journal:  Clin Microbiol Rev       Date:  2012-10       Impact factor: 26.132

5.  Toll-like receptor 9 and 21 have different ligand recognition profiles and cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish.

Authors:  Da-Wei Yeh; Yi-Ling Liu; Yin-Chiu Lo; Chiou-Hwa Yuh; Guann-Yi Yu; Jeng-Fan Lo; Yunping Luo; Rong Xiang; Tsung-Hsien Chuang
Journal:  Proc Natl Acad Sci U S A       Date:  2013-11-26       Impact factor: 11.205

6.  TLR-9 activation of marginal zone B cells in lupus mice regulates immunity through increased IL-10 production.

Authors:  Petar Lenert; Rachel Brummel; Elizabeth H Field; Robert F Ashman
Journal:  J Clin Immunol       Date:  2005-01       Impact factor: 8.317

Review 7.  DNA-stimulated cell death: implications for host defence, inflammatory diseases and cancer.

Authors:  Søren R Paludan; Line S Reinert; Veit Hornung
Journal:  Nat Rev Immunol       Date:  2019-03       Impact factor: 53.106

8.  Immunogenicity and efficacy of Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan peptide mimotope-protein conjugates in human immunoglobulin transgenic mice.

Authors:  Robert W Maitta; Kausik Datta; Andrew Lees; Shelley Sims Belouski; Liise-anne Pirofski
Journal:  Infect Immun       Date:  2004-01       Impact factor: 3.441

Review 9.  Traditional biochemical assays for studying toll-like receptor 9.

Authors:  Cynthia A Leifer; William A Rose; Fernando Botelho
Journal:  J Immunoassay Immunochem       Date:  2013

10.  Gangliosides trigger inflammatory responses via TLR4 in brain glia.

Authors:  Ilo Jou; Jee Hoon Lee; Soo Young Park; Hee Jung Yoon; Eun-Hye Joe; Eun Jung Park
Journal:  Am J Pathol       Date:  2006-05       Impact factor: 4.307

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