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

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, Slavena Vylkova, Gianni Panagiotou, Johannes Schumacher () and Oliver Kurzai ()
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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
Vitalia Schüller: University of Bonn, School of Medicine & University Hospital Bonn
Timo Hess: Philipps University of Marburg
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
Kerstin Hünniger: Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute
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
Johannes Schumacher: Philipps University of Marburg
Oliver Kurzai: Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-38994-5

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