Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-357441
- 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 affectInnate 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.…
Autor(en): | 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, Oliver Kurzai |
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URN: | urn:nbn:de:bvb:20-opus-357441 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Hygiene und Mikrobiologie |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Nature Communications |
Erscheinungsjahr: | 2023 |
Band / Jahrgang: | 14 |
Aufsatznummer: | 3239 |
Originalveröffentlichung / Quelle: | Nature Communications (2023) 14:3239. https://doi.org/10.1038/s41467-023-38994-5 Download citation |
DOI: | https://doi.org/10.1038/s41467-023-38994-5 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | antimicrobial responses; immunogenetics |
Datum der Freischaltung: | 30.04.2024 |
EU-Projektnummer / Contract (GA) number: | 847507 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |