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Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes

Author

Listed:
  • Sarah Kim

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn
    Institute of Molecular Medicine, University of Bonn)

  • Jessica Becker

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Matthias Bechheim

    (Institute of Molecular Medicine, University of Bonn)

  • Vera Kaiser

    (Institute of Molecular Medicine, University of Bonn)

  • Mahdad Noursadeghi

    (University College London)

  • Nadine Fricker

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Esther Beier

    (Institute of Molecular Medicine, University of Bonn)

  • Sven Klaschik

    (University of Bonn)

  • Peter Boor

    (University Clinic of RWTH Aachen)

  • Timo Hess

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Andrea Hofmann

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Stefan Holdenrieder

    (Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn)

  • Jens R. Wendland

    (Worldwide R&D, Pfizer Inc.)

  • Holger Fröhlich

    (Bonn-Aachen International Center for IT (B-IT), University of Bonn)

  • Gunther Hartmann

    (Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn)

  • Markus M. Nöthen

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Bertram Müller-Myhsok

    (Statistical Genetics, Max Planck Institute of Psychiatry
    Munich Cluster for Systems Neurology (SyNergy)
    Institute of Translational Medicine, University of Liverpool)

  • Benno Pütz

    (Statistical Genetics, Max Planck Institute of Psychiatry)

  • Veit Hornung

    (Institute of Molecular Medicine, University of Bonn)

  • Johannes Schumacher

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

Abstract

Toll-like receptors (TLRs) play a key role in innate immunity. Apart from their function in host defense, dysregulation in TLR signalling can confer risk to autoimmune diseases, septic shock or cancer. Here we report genetic variants and transcripts that are active only during TLR signalling and contribute to interindividual differences in immune response. Comparing unstimulated versus TLR4-stimulated monocytes reveals 1,471 expression quantitative trait loci (eQTLs) that are unique to TLR4 stimulation. Among these we find functional SNPs for the expression of NEU4, CCL14, CBX3 and IRF5 on TLR4 activation. Furthermore, we show that SNPs conferring risk to primary biliary cirrhosis (PBC), inflammatory bowel disease (IBD) and celiac disease are immune response eQTLs for PDGFB and IL18R1. Thus, PDGFB and IL18R1 represent plausible candidates for studying the pathophysiology of these disorders in the context of TLR4 activation. In summary, this study presents novel insights into the genetic basis of the innate immune response and exemplifies the value of eQTL studies in the context of exogenous cell stimulation.

Suggested Citation

  • Sarah Kim & Jessica Becker & Matthias Bechheim & Vera Kaiser & Mahdad Noursadeghi & Nadine Fricker & Esther Beier & Sven Klaschik & Peter Boor & Timo Hess & Andrea Hofmann & Stefan Holdenrieder & Jens, 2014. "Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes," Nature Communications, Nature, vol. 5(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6236
    DOI: 10.1038/ncomms6236
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    Cited by:

    1. Antje Häder & Sascha Schäuble & Jan Gehlen & Nadja Thielemann & Benedikt C. Buerfent & Vitalia Schüller & Timo Hess & Thomas Wolf & Julia Schröder & Michael Weber & Kerstin Hünniger & Jürgen Löffler &, 2023. "Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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