TY - JOUR
T1 - Borrelia burgdorferi Is a Poor Inducer of Gamma Interferon
T2 - Amplification Induced by Interleukin-12
AU - van de Schoor, Frederik R.
AU - Vrijmoeth, Hedwig D.
AU - Brouwer, Michelle A. E.
AU - ter Hofstede, Hadewych J. M.
AU - Lemmers, Heidi L. M.
AU - Dijkstra, Helga
AU - Boahen, Collins K.
AU - Oosting, Marije
AU - Kullberg, Bart-Jan
AU - Hovius, Joppe W.
AU - van den Wijngaard, Cees C.
AU - van de Veerdonk, Frank L.
AU - Netea, Mihai G.
AU - Joosten, Leo A. B.
N1 - Funding Information: F.R.V.D.S., H.D.V., M.A.E.B., B.J.K., J.W.H., C.C.V.D.W., and L.A.B.J. are funded by the Netherlands Organization for Health Research and Development (ZonMw, project numbers 200330008, 522050001, 522001003, 522050002, 522050003), which has peer-reviewed the grant application. J.W.H. is supported by INTERREG as part of the NorthTick project. M.G.N. was supported by an ERC Advanced Grant (#833247) and a Spinoza grant from the Netherlands Organization for Scientific Research (NWO). Publisher Copyright: Copyright © 2022 American Society for Microbiology. All Rights Reserved.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Laboratory diagnosis of Lyme borreliosis (LB) is mainly based on serology, which has limitations, particularly in the early stages of the disease. In recent years there have been conflicting reports concerning a new diagnostic tool using the cytokine interferon-gamma (IFN-g). Previous studies have generally found low concentrations of IFN-g in early LB infection. The goal of this study is to investigate IFN-g regulation during early LB and provide insights into the host response to B. burgdorferi. We performed in vitro experiments with whole blood assays and peripheral blood mononuclear cells (PBMCs) of LB patients and healthy volunteers exposed to B. burgdorferi and evaluated the IFN-g response using ELISA and related interindividual variation in IFN-g production to the presence of single nucleotide polymorphisms. IFN-g production of B. burgdorferi-exposed PBMCs and whole blood was amplified by the addition of interleukin-12 (IL-12) to the stimulation system. This effect was observed after 24 h of B. burgdorferi stimulation in both healthy individuals and LB patients. The effect was highly variable between individuals, but was significantly higher in LB patients 6 weeks since the start of antibiotic treatment compared to healthy individuals. IL-12 p40 and IL-18 mRNA were upregulated upon exposure to B. burgdorferi, whereas IL-12 p35 and IFN-g mRNA expression remained relatively unchanged. SNP Rs280520 in the downstream IL-12 pathway, Tyrosine Kinase 2, was associated with increased IFN-g production. This study shows that IL-12 evokes an IFN-g response in B. burgdorferi exposed cells, and that LB patients and healthy controls respond differently to this stimulation.
AB - Laboratory diagnosis of Lyme borreliosis (LB) is mainly based on serology, which has limitations, particularly in the early stages of the disease. In recent years there have been conflicting reports concerning a new diagnostic tool using the cytokine interferon-gamma (IFN-g). Previous studies have generally found low concentrations of IFN-g in early LB infection. The goal of this study is to investigate IFN-g regulation during early LB and provide insights into the host response to B. burgdorferi. We performed in vitro experiments with whole blood assays and peripheral blood mononuclear cells (PBMCs) of LB patients and healthy volunteers exposed to B. burgdorferi and evaluated the IFN-g response using ELISA and related interindividual variation in IFN-g production to the presence of single nucleotide polymorphisms. IFN-g production of B. burgdorferi-exposed PBMCs and whole blood was amplified by the addition of interleukin-12 (IL-12) to the stimulation system. This effect was observed after 24 h of B. burgdorferi stimulation in both healthy individuals and LB patients. The effect was highly variable between individuals, but was significantly higher in LB patients 6 weeks since the start of antibiotic treatment compared to healthy individuals. IL-12 p40 and IL-18 mRNA were upregulated upon exposure to B. burgdorferi, whereas IL-12 p35 and IFN-g mRNA expression remained relatively unchanged. SNP Rs280520 in the downstream IL-12 pathway, Tyrosine Kinase 2, was associated with increased IFN-g production. This study shows that IL-12 evokes an IFN-g response in B. burgdorferi exposed cells, and that LB patients and healthy controls respond differently to this stimulation.
KW - Antibody responses
KW - Borrelia
KW - Borreliosis
KW - Erythema migrans
KW - Interferon-gamma
KW - Lyme disease
UR - http://www.scopus.com/inward/record.url?scp=85126952411&partnerID=8YFLogxK
U2 - https://doi.org/10.1128/iai.00558-21
DO - https://doi.org/10.1128/iai.00558-21
M3 - Article
C2 - 35130450
SN - 0019-9567
VL - 90
JO - Infection and immunity
JF - Infection and immunity
IS - 3
M1 - e00558-21
ER -