A comprehensive genetic map of cytokine responses in Lyme borreliosis

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 Werfel, Thomas F. Schulz, Cheng-Jian Xu, Mihai G. Netea, Joppe W. Hovius, Leo A. B. Joosten and Yang Li ()
Additional contact information
Javier Botey-Bataller: Radboud university medical center
Hedwig D. Vrijmoeth: Radboud university medical center
Jeanine Ursinus: Center for Infectious Disease Control
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
Manoj K. Gupta: a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research
Lennart M. Roesner: Hannover Medical School
Jochen Huehn: Hannover Medical School
Thomas Werfel: Hannover Medical School
Thomas F. Schulz: Hannover Medical School
Cheng-Jian Xu: Radboud university medical center
Mihai G. Netea: Radboud university medical center
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
Yang Li: Radboud university medical center

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47505-z

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