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Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity

Author

Listed:
  • Antje Häder

    (Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute)

  • Sascha Schäuble

    (Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute)

  • Jan Gehlen

    (Philipps University of Marburg)

  • Nadja Thielemann

    (Julius Maximilians University of Wuerzburg)

  • Benedikt C. Buerfent

    (Philipps University of Marburg
    University of Bonn, School of Medicine & University Hospital Bonn)

  • Vitalia Schüller

    (University of Bonn, School of Medicine & University Hospital Bonn)

  • Timo Hess

    (Philipps University of Marburg
    University of Bonn, School of Medicine & University Hospital Bonn)

  • Thomas Wolf

    (Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute)

  • Julia Schröder

    (University of Bonn, School of Medicine & University Hospital Bonn)

  • Michael Weber

    (Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute
    Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute
    Friedrich-Loeffler-Institute)

  • Kerstin Hünniger

    (Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute
    Julius Maximilians University of Wuerzburg)

  • Jürgen Löffler

    (University Hospital Wuerzburg)

  • Slavena Vylkova

    (Septomics Research Center and Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute)

  • Gianni Panagiotou

    (Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute
    Friedrich Schiller University
    University of Hong Kong)

  • Johannes Schumacher

    (Philipps University of Marburg
    University of Bonn, School of Medicine & University Hospital Bonn)

  • Oliver Kurzai

    (Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute
    Julius Maximilians University of Wuerzburg)

Abstract

Innate immune responses vary by pathogen and host genetics. We analyze quantitative trait loci (eQTLs) and transcriptomes of monocytes from 215 individuals stimulated by fungal, Gram-negative or Gram-positive bacterial pathogens. We identify conserved monocyte responses to bacterial pathogens and a distinct antifungal response. These include 745 response eQTLs (reQTLs) and corresponding genes with pathogen-specific effects, which we find first in samples of male donors and subsequently confirm for selected reQTLs in females. reQTLs affect predominantly upregulated genes that regulate immune response via e.g., NOD-like, C-type lectin, Toll-like and complement receptor-signaling pathways. Hence, reQTLs provide a functional explanation for individual differences in innate response patterns. Our identified reQTLs are also associated with cancer, autoimmunity, inflammatory and infectious diseases as shown by external genome-wide association studies. Thus, reQTLs help to explain interindividual variation in immune response to infection and provide candidate genes for variants associated with a range of diseases.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38994-5
    DOI: 10.1038/s41467-023-38994-5
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    References listed on IDEAS

    as
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