Affiliation:
1. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
2. Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark
3. Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Copenhagen, Denmark
Abstract
ABSTRACT
Innate immune memory, or trained immunity, has recently been described to be an important property of cells of the innate immune system. Due to the increased interest in this important new field of immunological investigation, we sought to determine the optimal conditions for an
in vitro
experimental protocol of monocyte training using three of the most commonly used training stimuli from the literature: β-glucan, the bacillus Calmette-Guérin (BCG) vaccine, and oxidized low-density lipoprotein (oxLDL). We investigated and optimized a protocol of monocyte trained immunity induced by an initial training period with β-glucan, BCG, or oxLDL, followed by washing and resting of the cells and, thereafter, restimulation with secondary bacterial stimuli. The training and resting time intervals were varied to identify the optimal setting for the long-term induction of trained immunity. Trained immunity was assessed in terms of the secondary cytokine response, the production of reactive oxygen species, cell morphology, and induction of glycolysis. Monocytes primed with β-glucan, BCG, and oxLDL showed increased pro- and anti-inflammatory cytokine responses upon restimulation with nonrelated stimuli. Also, all three stimuli induced a switch to glycolysis (the Warburg effect). These effects were most pronounced when the training interval was 24 h and the resting time interval was 6 days. Training with BCG and oxLDL also led to the increased production of reactive oxygen species, whereas training with β-glucan led to the decreased production of reactive oxygen species. We describe the optimal conditions for an
in vitro
experimental model with human primary monocytes for study of the induction of trained innate immunity by microbial and metabolic stimuli.
Funder
Netherlands Heart Foundation
Netherlands Organization for Scientific Research
European Union Seventh Framework Programma
Dutch Arthritis Foundation
EC | European Research Council
EC | Horizon 2020
Publisher
American Society for Microbiology
Subject
Microbiology (medical),Clinical Biochemistry,Immunology,Immunology and Allergy
Cited by
222 articles.
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