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Veterinary research2013; 44(1); 50; doi: 10.1186/1297-9716-44-50

The molecular basis for recognition of bacterial ligands at equine TLR2, TLR1 and TLR6.

Abstract: TLR2 recognises bacterial lipopeptides and lipoteichoic acid, and forms heterodimers with TLR1 or TLR6. TLR2 is relatively well characterised in mice and humans, with published crystal structures of human TLR2/1/Pam3CSK4 and murine TLR2/6/Pam2CSK4. Equine TLR4 is activated by a different panel of ligands to human and murine TLR4, but less is known about species differences at TLR2. We therefore cloned equine TLR2, TLR1 and TLR6, which showed over 80% sequence identity with these receptors from other mammals, and performed a structure-function analysis. TLR2/1 and TLR2/6 from both horses and humans dose-dependently responded to lipoteichoic acid from Staphylococcus aureus, with no significant species difference in EC50 at either receptor pair. The EC50 of Pam2CSK4 was the same for equine and human TLR2/6, indicating amino acid differences between the two species' TLRs do not significantly affect ligand recognition. Species differences were seen between the responses to Pam2CSK4 and Pam3CSK4 at TLR2/1. Human TLR2/1, as expected, responded to Pam3CSK4 with greater potency and efficacy than Pam2CSK4. At equine TLR2/1, however, Pam3CSK4 was less potent than Pam2CSK4, with both ligands having similar efficacies. Molecular modelling indicates that the majority of non-conserved ligand-interacting residues are at the periphery of the TLR2 binding pocket and in the ligand peptide-interacting regions, which may cause subtle effects on ligand positioning. These results suggest that there are potentially important species differences in recognition of lipopeptides by TLR2/1, which may affect how the horse deals with bacterial infections.
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Publication Date: 2013-07-04 PubMed ID: 23826682PubMed Central: PMC3716717DOI: 10.1186/1297-9716-44-50Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the molecular basis of bacterial detection in horses, specifically through three types of Toll-like receptors (TLRs): TLR2, TLR1, and TLR6. It found that despite some species differences between horses and humans, these receptors in both species responded similarly to certain bacterial substances, suggesting they play a vital role in bacterial infection response.

Introduction and Purpose

  • The research aimed to understand how equine TLR2, TLR1, and TLR6 recognize bacterial ligands, substances that can cause an immune response.
  • The study was sparked by the knowledge that TLR4 activates differently in horses than in humans and mice, suggesting there might be species differences in the TLR2 receptor set as well.
  • Understanding these differences could have significance for how horses deal with bacterial infections.

Methodology

  • The researchers cloned the equine TLR2, TLR1, and TLR6 and conducted a structure-function analysis.
  • They gathered sequence identity information between the equine receptors and those of other mammals which appeared to show over 80% similarity.

Findings

  • TLR2/1 and TLR2/6 pairs from both horses and humans exhibited a dose-dependent response to lipoteichoic acid from Staphylococcus aureus and showed no significant species difference in EC50, the dosage concentration which triggers a half-max response.
  • The researchers found no significant differences in ligand recognition due to amino acid differences between human and horse TLRs when tested with Pam2CSK4, a synthetic bacterial lipopeptide.
  • There were differences observed between the response of human and horse TLR2/1 to two synthetic lipopeptides, Pam2CSK4 and Pam3CSK4. The human TLR2/1 responded to Pam3CSK4 more potently and efficiently than Pam2CSK4, while the horse TLR2/1 showed less potency for Pam3CSK4 than Pam2CSK4.
  • Molecular modelling suggested the occurrence of some non-conserved ligand-interacting residues, which might impact ligand positioning.

Conclusion

  • The study concluded that important species differences exist in lipopeptide recognition by TLR2/1, potentially influencing the equine response to bacterial infections.

Cite This Article

APA
Irvine KL, Hopkins LJ, Gangloff M, Bryant CE. (2013). The molecular basis for recognition of bacterial ligands at equine TLR2, TLR1 and TLR6. Vet Res, 44(1), 50. https://doi.org/10.1186/1297-9716-44-50

Publication

Veterinary research
ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English
Volume: 44
Issue: 1
Pages: 50

Researcher Affiliations

Irvine, Katherine Lucy
  • Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB30ES, UK. ceb27@cam.ac.uk.
Hopkins, Lee Jason
    Gangloff, Monique
      Bryant, Clare Elizabeth

        MeSH Terms

        • Animals
        • HEK293 Cells
        • Horses / genetics
        • Horses / metabolism
        • Humans
        • Ligands
        • Lipopeptides / metabolism
        • Lipopolysaccharides / metabolism
        • Mice
        • Molecular Conformation
        • Reverse Transcriptase Polymerase Chain Reaction / veterinary
        • Staphylococcus aureus / physiology
        • Teichoic Acids / metabolism
        • Toll-Like Receptor 1 / chemistry
        • Toll-Like Receptor 1 / genetics
        • Toll-Like Receptor 1 / metabolism
        • Toll-Like Receptor 2 / chemistry
        • Toll-Like Receptor 2 / genetics
        • Toll-Like Receptor 2 / metabolism
        • Toll-Like Receptor 6 / chemistry
        • Toll-Like Receptor 6 / genetics
        • Toll-Like Receptor 6 / metabolism

        Grant Funding

        • Biotechnology and Biological Sciences Research Council
        • Wellcome Trust

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