IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38994-5.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38994-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38994-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Olivier Delaneau & Halit Ongen & Andrew A. Brown & Alexandre Fort & Nikolaos I. Panousis & Emmanouil T. Dermitzakis, 2017. "A complete tool set for molecular QTL discovery and analysis," Nature Communications, Nature, vol. 8(1), pages 1-7, August.
    2. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    3. 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.
    4. Carl D. Langefeld & Hannah C. Ainsworth & Deborah S. Cunninghame Graham & Jennifer A. Kelly & Mary E. Comeau & Miranda C. Marion & Timothy D. Howard & Paula S. Ramos & Jennifer A. Croker & David L. Mo, 2017. "Transancestral mapping and genetic load in systemic lupus erythematosus," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
    5. Sarah Kim-Hellmuth & Matthias Bechheim & Benno Pütz & Pejman Mohammadi & Yohann Nédélec & Nicholas Giangreco & Jessica Becker & Vera Kaiser & Nadine Fricker & Esther Beier & Peter Boor & Stephane E. C, 2017. "Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Satria P. Sajuthi & Jamie L. Everman & Nathan D. Jackson & Benjamin Saef & Cydney L. Rios & Camille M. Moore & Angel C. Y. Mak & Celeste Eng & Ana Fairbanks-Mahnke & Sandra Salazar & Jennifer Elhawary, 2022. "Nasal airway transcriptome-wide association study of asthma reveals genetically driven mucus pathobiology," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Anneke Brümmer & Sven Bergmann, 2024. "Disentangling genetic effects on transcriptional and post-transcriptional gene regulation through integrating exon and intron expression QTLs," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Andrew A. Brown & Juan J. Fernandez-Tajes & Mun-gwan Hong & Caroline A. Brorsson & Robert W. Koivula & David Davtian & Théo Dupuis & Ambra Sartori & Theodora-Dafni Michalettou & Ian M. Forgie & Jonath, 2023. "Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Angela Andaleon & Lauren S Mogil & Heather E Wheeler, 2019. "Genetically regulated gene expression underlies lipid traits in Hispanic cohorts," PLOS ONE, Public Library of Science, vol. 14(8), pages 1-21, August.
    5. Lei Li & Xuelian Ma & Ya Cui & Maxime Rotival & Wenyan Chen & Xudong Zou & Ruofan Ding & Yangmei Qin & Qixuan Wang & Lluis Quintana-Murci & Wei Li, 2023. "Immune-response 3′UTR alternative polyadenylation quantitative trait loci contribute to variation in human complex traits and diseases," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Xena Marie Mapel & Naveen Kumar Kadri & Alexander S. Leonard & Qiongyu He & Audald Lloret-Villas & Meenu Bhati & Maya Hiltpold & Hubert Pausch, 2024. "Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. Tina Roostaei & Hans-Ulrich Klein & Yiyi Ma & Daniel Felsky & Pia Kivisäkk & Sarah M. Connor & Alexandra Kroshilina & Christina Yung & Belinda J. Kaskow & Xiaorong Shao & Brooke Rhead & José M. Ordová, 2021. "Proximal and distal effects of genetic susceptibility to multiple sclerosis on the T cell epigenome," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    8. Sébastien Thériault & Zhonglin Li & Erik Abner & Jian’an Luan & Hasanga D. Manikpurage & Ursula Houessou & Pardis Zamani & Mewen Briend & Dominique K. Boudreau & Nathalie Gaudreault & Lily Frenette & , 2024. "Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Jayshree Advani & Puja A. Mehta & Andrew R. Hamel & Sudeep Mehrotra & Christina Kiel & Tobias Strunz & Ximena Corso-Díaz & Madeline Kwicklis & Freekje Asten & Rinki Ratnapriya & Emily Y. Chew & Dena G, 2024. "QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    10. James J. Gilchrist & Seiko Makino & Vivek Naranbhai & Piyush K. Sharma & Surya Koturan & Orion Tong & Chelsea A. Taylor & Robert A. Watson & Alba Verge los Aires & Rosalin Cooper & Evelyn Lau & Sara D, 2022. "Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    12. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Julia Schröder & Vitalia Schüller & Andrea May & Christian Gerges & Mario Anders & Jessica Becker & Timo Hess & Nicole Kreuser & René Thieme & Kerstin U Ludwig & Tania Noder & Marino Venerito & Lothar, 2019. "Identification of loci of functional relevance to Barrett’s esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with gen," PLOS ONE, Public Library of Science, vol. 14(12), pages 1-12, December.
    14. Lili Liu & Atlas Khan & Elena Sanchez-Rodriguez & Francesca Zanoni & Yifu Li & Nicholas Steers & Olivia Balderes & Junying Zhang & Priya Krithivasan & Robert A. LeDesma & Clara Fischman & Scott J. Heb, 2022. "Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    15. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    16. Brittany L. Mitchell & Jake R. Saklatvala & Nick Dand & Fiona A. Hagenbeek & Xin Li & Josine L. Min & Laurent Thomas & Meike Bartels & Jouke Hottenga & Michelle K. Lupton & Dorret I. Boomsma & Xianjun, 2022. "Genome-wide association meta-analysis identifies 29 new acne susceptibility loci," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    17. Zichen Zhang & Ye Eun Bae & Jonathan R. Bradley & Lang Wu & Chong Wu, 2022. "SUMMIT: An integrative approach for better transcriptomic data imputation improves causal gene identification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    18. Pietro Demela & Nicola Pirastu & Blagoje Soskic, 2023. "Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    19. Zhaotong Lin & Wei Pan, 2024. "A robust cis-Mendelian randomization method with application to drug target discovery," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    20. Yuandan Wei & Jianxin Zhen & Liang Hu & Yuqin Gu & Yanhong Liu & Xinxin Guo & Zijing Yang & Hao Zheng & Shiyao Cheng & Fengxiang Wei & Likuan Xiong & Siyang Liu, 2024. "Genome-wide association studies of thyroid-related hormones, dysfunction, and autoimmunity among 85,421 Chinese pregnancies," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38994-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.