TY - JOUR
T1 - A comprehensive genetic map of cytokine responses in Lyme borreliosis
AU - Botey-Bataller, Javier
AU - Vrijmoeth, Hedwig D.
AU - Ursinus, Jeanine
AU - Kullberg, Bart-Jan
AU - van den Wijngaard, Cees C.
AU - ter Hofstede, Hadewych
AU - Alaswad, Ahmed
AU - Gupta, Manoj K.
AU - Roesner, Lennart M.
AU - Huehn, Jochen
AU - Werfel, Thomas
AU - Schulz, Thomas F.
AU - Xu, Cheng-Jian
AU - Netea, Mihai G.
AU - Hovius, Joppe W.
AU - Joosten, Leo A. B.
AU - Li, Yang
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024/12/1
Y1 - 2024/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85192222937&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-47505-z
DO - 10.1038/s41467-024-47505-z
M3 - Article
C2 - 38714679
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3795
ER -