- Immune responses and vaccinations
- Epigenetics and DNA Methylation
- Immune cells in cancer
- COVID-19 Impact on Reproduction
- Diabetes and associated disorders
- Tryptophan and brain disorders
- Vaccine Coverage and Hesitancy
- Immunodeficiency and Autoimmune Disorders
- Bladder and Urothelial Cancer Treatments
- Reproductive System and Pregnancy
- Immunotherapy and Immune Responses
- Zoonotic diseases and public health
- Neonatal Respiratory Health Research
- Phagocytosis and Immune Regulation
- SARS-CoV-2 and COVID-19 Research
Radboud University Nijmegen
2019-2023
Radboud University Medical Center
2019-2023
Radboud Institute for Molecular Life Sciences
2019-2022
University Medical Center
2021
Trained immunity confers a sustained augmented response of innate immune cells to secondary challenge, via process dependent on metabolic and transcriptional reprogramming. Because its previous associations with memory, as well the importance H3 histone lysine 4 monomethylation (H3K4me1) we hypothesize that Set7 methyltransferase has an important role in trained induced by β-glucan. Using pharmacological studies human primary monocytes, identify immunity-specific immunometabolic pathways...
Abstract Stimulation of monocytes with microbial and non-microbial products, including oxidized low-density lipoprotein (oxLDL), induces a protracted pro-inflammatory, atherogenic phenotype sustained by metabolic epigenetic reprogramming via process called trained immunity . We investigated the intracellular mechanisms driving oxLDL-induced in human primary observed concomitant upregulation glycolytic activity oxygen consumption. In two separate cohorts healthy volunteers, we assessed impact...
A growing number of studies show that innate immune cells can undergo functional reprogramming, facilitating a faster and enhanced response to heterologous secondary stimuli. This concept has been termed "trained immunity." We outline here protocol recapitulate this in vitro using adherent monocytes from consecutive isolation peripheral blood mononuclear cells. The induction trained immunity the associated reprogramming is described detail β-glucan (from Candida albicans) Bacillus...
BCG is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it unknown whether application induces trained immunity.The aim this research was determine immunity NMIBC patients. We conducted a prospective observational cohort study 17 scheduled for therapy and measured parameters at 9 time points before during 1-year maintenance regimen. Ex vivo cytokine production by peripheral blood...
Abstract Following brief exposure to endogenous atherogenic particles, such as oxidized low-density lipoprotein (oxLDL), monocytes/macrophages can adopt a long-term pro-inflammatory phenotype, which is called trained immunity. This mechanism might contribute the chronic low-grade inflammation that characterizes atherosclerosis. In this study, we aim elucidate immunometabolic pathways drive oxLDL-induced Primary isolated human monocytes were exposed oxLDL for 24 h, and after five days...
Summary Toll‐like receptor 10 (TLR10) is the only member of human family with an inhibitory function on induction innate immune responses and inflammation. However, its role in modulation trained immunity (innate memory) unknown. In present study, we assessed whether TLR10 modulates induced by β ‐glucan or bacillus Calmette–Guérin (BCG). Interleukin antagonist production was increased upon activation ex vivo after BCG vaccination, protein expression monocytes whereas anti‐TLR10 antibodies...
Histone methyltransferase G9a, also known as Euchromatic Lysine Methyltransferase 2 (EHMT2), mediates H3K9 methylation which is associated with transcriptional repression. It possesses immunomodulatory effects and overexpressed in multiple types of cancer. In this study, we investigated the role G9a induction trained immunity, a de facto innate immune memory, its non-muscle-invasive bladder cancer (NMIBC) patients treated intravesical Bacillus Calmette-Guérin (BCG).EHMT2 expression was...
Abstract Atherosclerotic cardiovascular diseases (CVD) are among the leading causes of death in world. Monocyte-derived macrophages key players pathophysiology atherosclerosis. Innate immune memory following exposure monocytes to atherogenic compounds, such as oxidized low-density lipoproteins (oxLDL), termed trained immunity, can contribute atherogenesis. The current study aimed elucidate intracellular mechanisms oxLDL-induced immunity. Using untargeted metabolomics isolated human primary...
Sirtuin 1 (SIRT1) has been described to modify immune responses by modulation of gene transcription. As transcriptional reprogramming is the molecular substrate trained immunity, a de facto innate memory, we investigated role SIRT1 in induction immunity. We identified various genetic single nucleotide polymorphisms affecting and adaptive cytokine production human peripheral blood mononuclear cells (PBMCs) response stimuli on one hand, vitro immunity other hand. Furthermore, inhibition...
Abstract Bacillus Calmette-Guérin (BCG) is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it unknown whether BCG application induces trained immunity. Here, we found that does induce immunity based on an increased production TNF and IL-1β after heterologous ex-vivo stimulation circulating monocytes 6- 12 weeks treatment; a 37% decreased (OR 0.63 (95% CI 0.40- 1.01)) for respiratory...