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A comprehensive genetic map of cytokine responses in Lyme borreliosis

Author

Listed:
  • Javier Botey-Bataller

    (Radboud university medical center
    a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research
    a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research)

  • Hedwig D. Vrijmoeth

    (Radboud university medical center
    Center for Infectious Disease Control)

  • Jeanine Ursinus

    (Center for Infectious Disease Control
    Division of Infectious Diseases & Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam)

  • Bart-Jan Kullberg

    (Radboud university medical center)

  • Cees C. Wijngaard

    (Center for Infectious Disease Control)

  • Hadewych Hofstede

    (Radboud university medical center)

  • Ahmed Alaswad

    (a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research
    a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research)

  • Manoj K. Gupta

    (a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research
    a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research
    Hannover Medical School)

  • Lennart M. Roesner

    (Hannover Medical School
    Hannover Medical School)

  • Jochen Huehn

    (Hannover Medical School
    Helmholtz Centre for Infection Research)

  • Thomas Werfel

    (Hannover Medical School
    Hannover Medical School)

  • Thomas F. Schulz

    (Hannover Medical School
    Hannover Medical School)

  • Cheng-Jian Xu

    (Radboud university medical center
    a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research
    a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research)

  • Mihai G. Netea

    (Radboud university medical center
    University of Bonn)

  • Joppe W. Hovius

    (Division of Infectious Diseases & Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam)

  • Leo A. B. Joosten

    (Radboud university medical center
    Iuliu Hatieganu University of Medicine and Pharmacy)

  • Yang Li

    (Radboud university medical center
    a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research
    a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research
    Hannover Medical School)

Abstract

The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.

Suggested Citation

  • Javier Botey-Bataller & Hedwig D. Vrijmoeth & Jeanine Ursinus & Bart-Jan Kullberg & Cees C. Wijngaard & Hadewych Hofstede & Ahmed Alaswad & Manoj K. Gupta & Lennart M. Roesner & Jochen Huehn & Thomas , 2024. "A comprehensive genetic map of cytokine responses in Lyme borreliosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47505-z
    DOI: 10.1038/s41467-024-47505-z
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    as
    1. Benjamin B. Sun & Joshua Chiou & Matthew Traylor & Christian Benner & Yi-Hsiang Hsu & Tom G. Richardson & Praveen Surendran & Anubha Mahajan & Chloe Robins & Steven G. Vasquez-Grinnell & Liping Hou & , 2023. "Plasma proteomic associations with genetics and health in the UK Biobank," Nature, Nature, vol. 622(7982), pages 329-338, October.
    2. Marisa W. Friederich & Sharita Timal & Christopher A. Powell & Cristina Dallabona & Alina Kurolap & Sara Palacios-Zambrano & Drago Bratkovic & Terry G. J. Derks & David Bick & Katelijne Bouman & Kathr, 2018. "Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    3. 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.
    4. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "Author Correction: FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 615(7952), pages 19-19, March.
    5. Gao Wang & Abhishek Sarkar & Peter Carbonetto & Matthew Stephens, 2020. "A simple new approach to variable selection in regression, with application to genetic fine mapping," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 82(5), pages 1273-1300, December.
    6. Hema Adhikari & Walaa E. Kattan & Shivesh Kumar & Pei Zhou & John F. Hancock & Christopher M. Counter, 2021. "Oncogenic KRAS is dependent upon an EFR3A-PI4KA signaling axis for potent tumorigenic activity," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    7. Makoto Kuro-o & Yutaka Matsumura & Hiroki Aizawa & Hiroshi Kawaguchi & Tatsuo Suga & Toshihiro Utsugi & Yoshio Ohyama & Masahiko Kurabayashi & Tadashi Kaname & Eisuke Kume & Hitoshi Iwasaki & Akihiro , 1997. "Mutation of the mouse klotho gene leads to a syndrome resembling ageing," Nature, Nature, vol. 390(6655), pages 45-51, November.
    8. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
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