An Explorative Study on Monocyte Reprogramming in the Context of Periodontitis In Vitro and In Vivo .
| Autor: | Noz MP; Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands., Plachokova AS; Department of Dentistry, Radboud University Medical Center, Nijmegen, Netherlands., Smeets EMM; Department of Radiology, Nuclear Medicine and Anatomy, Radboud University Medical Center, Nijmegen, Netherlands., Aarntzen EHJG; Department of Radiology, Nuclear Medicine and Anatomy, Radboud University Medical Center, Nijmegen, Netherlands., Bekkering S; Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands., Vart P; Department of Health Evidence and Radboud Institute for Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, Netherlands., Joosten LAB; Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands.; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Netea MG; Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands.; Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany., Riksen NP; Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in immunology [Front Immunol] 2021 Aug 13; Vol. 12, pp. 695227. Date of Electronic Publication: 2021 Aug 13 (Print Publication: 2021). |
| DOI: | 10.3389/fimmu.2021.695227 |
| Abstrakt: | Aims: Periodontitis is an independent risk factor for cardiovascular disease, but the mechanistic link is not fully understood. In atherosclerotic cardiovascular disease, monocytes can adopt a persistent hyperresponsive phenotype, termed trained immunity. We hypothesized that periodontitis-associated bacteria can induce trained immunity in monocytes, which subsequently accelerate atherosclerosis development. Materials and Methods: We combined in vitro experiments on human primary monocytes and in vivo techniques in patients with periodontitis to test this hypothesis. Adherent peripheral blood mononuclear cells (PBMCs) were transiently exposed in vitro to Porphyromonas gingivalis for 24 hours, and restimulated with lipopolysaccharide (LPS) or Pam3CysK4 (P3C) six days later, to measure interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) production. In an exploratory observational study, patients with severe periodontitis (63 ± 6 years, n=14) and control subjects with no-to-mild periodontitis (54 ± 10 years, n=14) underwent venipuncture and 2'-deoxy-2'-[ 18 F]fluoro-D-glucose positron-emission-tomography ([ 18 F]FDG PET/CT) scanning. Results: When adherent peripheral blood mononuclear cells (PBMCs) were transiently exposed in vitro to Porphyromonas gingivalis for 24 hours, and restimulated with LPS or P3C six days later, IL-6 and TNFα production was significantly increased (TNFα/P3C, p<0.01). Circulating leukocytes, IL-6 and interleukin-1 receptor antagonist (IL-1Ra) concentrations were generally higher in patients compared to controls (leukocytes: p<0.01; IL-6: p=0.08; IL-1Ra: p=0.10). Cytokine production capacity in PBMCs after 24h stimulation revealed no differences between groups. [ 18 F]FDG PET/CT imaging showed a trend for increased [ 18 F]FDG-uptake in the periodontium [mean standard uptake value (SUV Conclusions: P. gingivalis induces long-term activation of human monocytes in vitro (trained immunity). Patients with severe periodontitis did have signs of increased systemic inflammation and hematopoietic tissue activation. However, their circulating monocytes did not show a hyperresponsive phenotype. Together we suggest that trained immunity might contribute to local periodontal inflammation which warrants further investigation. Competing Interests: LJ and MGN are scientific founders of TTxD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Noz, Plachokova, Smeets, Aarntzen, Bekkering, Vart, Joosten, Netea and Riksen.) |
| Databáze: | MEDLINE |
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