A5022140103- Immune responses and vaccinations
- Antifungal resistance and susceptibility
- HIV Research and Treatment
- Fungal Infections and Studies
- Epigenetics and DNA Methylation
- COVID-19 Impact on Reproduction
- HIV-related health complications and treatments
- Gut microbiota and health
- Immune Cell Function and Interaction
- Immune cells in cancer
- Diabetes and associated disorders
- Tryptophan and brain disorders
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Mental Health Research Topics
- Vaccine Coverage and Hesitancy
- IL-33, ST2, and ILC Pathways
- Inflammasome and immune disorders
- SARS-CoV-2 and COVID-19 Research
- HIV/AIDS Research and Interventions
- Diet and metabolism studies
- HIV/AIDS drug development and treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Radboud University Nijmegen
2019-2025
Radboud University Medical Center
2019-2025
University Medical Center
2021-2024
Radboud Institute for Molecular Life Sciences
2019-2023
University of Groningen
2014-2023
University Medical Center Groningen
2016-2021
General Hospital of Athens G. Genimatas
2017
Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate activation and memory that indicative immunity. We established personal profiles chromatin accessibility maps over a 90-day time course BCG vaccination in 323 Our...
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...
Biologics directed against the T-helper (Th)-17 pathway have been approved for several inflammatory diseases. Interleukin (IL)-17 is involved in anti-Candida host defense, and clinical trials suggested increased candidiasis incidence during IL-17 inhibitor therapy. We describe worldwide epidemiology of Th17 therapy, immunological mechanisms susceptibility. A comprehensive analysis multiple independent sources reporting Candida adverse events biologics inhibiting was performed. Association...
Abstract The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. disease severity correlates with an excessive proinflammatory immune profound lymphopenia. Inflammatory responses according to were explored by plasma cytokine measurements proteomics analysis 147 patients. Furthermore, peripheral blood mononuclear cell production assays whole flow cytometry performed. Results confirm a hyperinflammatory innate...
Trained immunity describes the capacity of innate immune cells to develop heterologous memory in response certain exogenous exposures. This phenomenon mediates, at least part, beneficial off-target effects BCG vaccine. Using an vitro model trained immunity, we show that exposure induces a persistent change active histone modifications, DNA methylation, transcription, and adenosine-to-inosine RNA modification human monocytes. By profiling methylation circulating monocytes from infants MIS...
Itaconate is an immunomodulatory metabolite produced by immune cells under microbial stimulation and certain pro-inflammatory conditions triggers antioxidant anti-inflammatory responses. We show that dimethyl itaconate, a derivative of itaconate previously linked to suppression inflammation widely employed as alternative the endogenous metabolite, can induce long-term transcriptional, epigenomic, metabolic changes, characteristic trained immunity. Dimethyl alters glycolytic mitochondrial...
Bacillus Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines worldwide. In addition to protection against tuberculosis, BCG confers a degree non-specific other infections by enhancing secondary immune responses heterologous pathogens, termed "trained immunity." To better understand BCG-induced reprogramming, we perform single-cell transcriptomic measurements before and after vaccination using stimulation with bacterial lipopolysaccharide (LPS). We find that reduces systemic...
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...
Immunological non-responders (INR) are people living with HIV (PLHIV) who fail to fully restore CD4+ T-cell counts despite complete viral suppression antiretroviral therapy (ART). INR at higher risk for non-HIV related morbidity and mortality. Previous research suggest persistent qualitative defects. The 2000HIV study (clinical trials NTC03994835) enrolled 1895 PLHIV, divided in a discovery validation cohort. PLHIV CD4 count <350 cells/mm3 after ≥2 years of suppressive ART were defined as...
Rewiring cellular metabolism is important for activation of immune cells during host defense against Mycobacterium tuberculosis. Glutamine has been implicated as an immunomodulatory nutrient, but its role in the response to M. tuberculosis unknown. We assessed expression glutamine pathway genes tuberculosis–infected macrophages and blood transcriptomic profiles individuals with latent infection or Subsequently, we studied effect blocking glutaminolysis on tuberculosis–induced cytokines....
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...
The innate immune system displays heterologous memory characteristics, which are characterized by stronger responses to a secondary challenge. This phenomenon termed trained immunity relies on epigenetic and metabolic rewiring of cells. As reactive oxygen species (ROS) production has been associated with the phenotype, we hypothesized that increased ROS levels main intracellular redox molecule glutathione play role in induction immunity. Here show pharmacological inhibition an vitro model...
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...
Due to the increased burden of non-AIDS-related comorbidities in people living with HIV (PLHIV), identifying biomarkers and mechanisms underlying premature aging risk developing age-related is a priority. Evidence suggests that plasma proteome an accurate source for measuring biological age predicting clinical outcomes. To investigate whether PLHIV on antiretroviral therapy (ART) exhibit phenotype, we profiled two independent cohorts virally suppressed (200HIV 2000HIV) one cohort without...
We assessed the role of immunogenetic background in development and recurrence acute idiopathic pericarditis (AIP).Fifty-five patients with a first episode AIP were followed for 23.8 ± 6.3 months recurrences recorded. The control group consisted 246 healthy individuals. In all subjects, genomic human leukocyte antigen (HLA) typing was performed. Moreover, circulating lymphocyte subpopulations studied 44 randomly selected 20 controls.An increased frequency HLA-A*02, -Cw*07 -DQB1*0202 alleles,...
Tetraspanins are a family of proteins possessing four transmembrane domains that help in lateral organization plasma membrane proteins. These interact with each other as well receptors and signaling proteins, resulting functional complexes called "tetraspanin microdomains." Tetraspanins, including CD82, play an essential role the pathogenesis fungal infections. Dectin-1, receptor for cell wall carbohydrate β-1,3-glucan, is vital to host defense against The current study identifies novel...
People living with human immunodeficiency virus (PLHIV) are exposed to chronic immune dysregulation, even when replication is suppressed by antiretroviral therapy (ART). Given the emerging role of gut microbiome in immunity, we hypothesized that may be related cytokine production capacity PLHIV.
Abstract Infections and vaccines can induce enhanced long-term responses in innate immune cells, establishing an immunological memory termed trained immunity . Here, we show that monocytes with a phenotype, due to exposure the Bacillus Calmette-Guérin (BCG) vaccine, are characterized by increased biosynthesis of different lipid mediators (LM) derived from long-chain polyunsaturated fatty acids (PUFA). Pharmacological genetic approaches PUFA synthesis lipoxygenase-derived LM essential for...