1. Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming
- Author
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Anette Christ, Laszlo Groh, Thomas Ulas, Terje Espevik, Kathrin Klee, Michael L. Fitzgerald, Peter Duewell, Debjani Biswas, Kevin Baßler, Marije Oosting, Vinod Kumar, Claus J. Scholz, Kristian Haendler, Mihai G. Netea, Simone J.C.F.M. Moorlag, Niels P. Riksen, Eicke Latz, Jonas Schulte-Schrepping, Min Hi Park, Leo A. B. Joosten, Joachim L. Schultze, Andreas Schlitzer, Karin Pelka, Mario A. Lauterbach, Yang Li, Patrick Günther, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
- Subjects
Male ,0301 basic medicine ,Myeloid ,Lipopolysaccharide ,metabolism [NLR Family, Pyrin Domain-Containing 3 Protein] ,Interleukin-1beta ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Systemic inflammation ,DISEASE ,Epigenesis, Genetic ,NLRP3 INFLAMMASOME ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,INTERLEUKIN-1 ,genetics [Receptors, LDL] ,FAMILIAL HYPERCHOLESTEROLEMIA ,Cells, Cultured ,GENE-EXPRESSION ,Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16] ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,NALP3 INFLAMMASOME ,Middle Aged ,Cellular Reprogramming ,3. Good health ,Lipoproteins, LDL ,medicine.anatomical_structure ,STEM-CELL PROLIFERATION ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,Reprogramming ,Adult ,Secondary infection ,Quantitative Trait Loci ,Nlrp3 protein, mouse ,Inflammation ,Biology ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Immunity ,Memory ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,Humans ,ddc:610 ,Aged ,genetics [NLR Family, Pyrin Domain-Containing 3 Protein] ,Innate immune system ,Macrophages ,Immunity, Innate ,Mice, Inbred C57BL ,030104 developmental biology ,Receptors, LDL ,chemistry ,HEMATOPOIETIC STEM ,MYOCARDIAL-INFARCTION ,ATHEROSCLEROSIS ,Diet, Western ,Immunology ,metabolism [Lipoproteins, LDL] ,Immunologic Memory ,immunology [Myeloid Cells] - Abstract
Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed "trained immunity,'' causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr(-/-) mice induced systemic inflammation, which was undetectable in serum soon after mice were shifted back to a chow diet (CD). In contrast, myeloid cell responses toward innate stimuli remained broadly augmented. WD-induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells led to increased proliferation and enhanced innate immune responses. Quantitative trait locus (QTL) analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with lipopolysaccharide (LPS) suggested inflammasome-mediated trained immunity. Consistently, Nlrp3(-/-)/Ldlr(-/-) mice lacked WD-induced systemic inflammation, myeloidprogenitor proliferation, and re-programming. Hence, NLRP3 mediates trained immunity following WD and could thereby mediate the potentially deleterious effects of trained immunity in inflammatory diseases.
- Published
- 2018
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