Borrelia burgdorferi Is a Poor Inducer of Gamma Interferon: Amplification Induced by Interleukin-12.

Autor: van de Schoor FR; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Vrijmoeth HD; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Brouwer MAE; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Ter Hofstede HJM; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Lemmers HLM; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Dijkstra H; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Boahen CK; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Oosting M; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Kullberg BJ; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Hovius JW; Amsterdam UMC, University of Amsterdam, Center for Experimental and Molecular Medicine, Amsterdam Institute of Infection and Immunology, Amsterdam, The Netherlands., van den Wijngaard CC; National Institute for Public Health and the Environment (RIVM), Center of Infectious Disease Control, Bilthoven, The Netherlands., van de Veerdonk FL; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Netea MG; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands.; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Germany., Joosten LAB; Radboudumc, Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI) and Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Infection and immunity [Infect Immun] 2022 Mar 17; Vol. 90 (3), pp. e0055821. Date of Electronic Publication: 2022 Feb 07.
DOI: 10.1128/iai.00558-21
Abstrakt: 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-γ). Previous studies have generally found low concentrations of IFN-γ in early LB infection. The goal of this study is to investigate IFN-γ 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-γ response using ELISA and related interindividual variation in IFN-γ production to the presence of single nucleotide polymorphisms. IFN-γ 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-γ mRNA expression remained relatively unchanged. SNP Rs280520 in the downstream IL-12 pathway, Tyrosine Kinase 2, was associated with increased IFN-γ production. This study shows that IL-12 evokes an IFN-γ response in B. burgdorferi exposed cells, and that LB patients and healthy controls respond differently to this stimulation.
Databáze: MEDLINE