- HIV Research and Treatment
- HIV-related health complications and treatments
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Diabetes and associated disorders
- Immunodeficiency and Autoimmune Disorders
- NF-κB Signaling Pathways
- Radioactive element chemistry and processing
- Platelet Disorders and Treatments
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Ubiquitin and proteasome pathways
- IL-33, ST2, and ILC Pathways
- Acute Myeloid Leukemia Research
- Sepsis Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Vector-borne infectious diseases
- Gut microbiota and health
- Viral-associated cancers and disorders
- Blood Coagulation and Thrombosis Mechanisms
- Mechanical Circulatory Support Devices
- Influenza Virus Research Studies
- Mosquito-borne diseases and control
- Radiation Detection and Scintillator Technologies
- Adrenal Hormones and Disorders
Radboud University Medical Center
2016-2024
Radboud University Nijmegen
2016-2024
Radboud Institute for Molecular Life Sciences
2023
ALS Centrum Nederland
1966
Chronic inflammation and immune dysfunction play a key role in the development of non-AIDS–related comorbidities. The aim our study was to characterize functional phenotype cells people living with HIV (PLHIV). We enrolled cross-sectional cohort PLHIV on stable antiretroviral therapy healthy controls. assessed ex vivo cytokine production capacity transcriptomics monocytes T upon bacterial, fungal, viral stimulation. exhibited an exacerbated proinflammatory profile monocyte-derived cytokines,...
Summary The use of acetylsalicylic acid (ASA) is associated with improved outcome in patients sepsis, and P2Y12 inhibitors have been suggested to also immunomodulatory effects. Therefore, we evaluated the effects clinically relevant combinations antiplatelet therapy on immune response experimental endotoxaemia humans vivo. Forty healthy subjects were randomised seven days placebo, placebo ASA, ticagrelor or clopidogrel ASA treatment. Systemic inflammation was elicited at day by intravenous...
Different components of the immune response show large variability between individuals, but they also vary within same individual because host and environmental factors. In this study, we report an extensive analysis characteristics 56 individuals over four timepoints in 1 single year as part Human Functional Genomics Project. We characterized 102 cell subsets using flow cytometry; quantified production eight cytokines two chemokines to 20 metabolic, bacterial, fungal, viral stimuli;...
Abstract Clonal hematopoiesis, a common age-related phenomenon marked by expansion of cells with clonal hematopoiesis driver mutations, has been associated all-cause mortality, cancer, and cardiovascular disease. People HIV (PWH) are at risk for non-AIDS–related comorbidities such as atherosclerotic disease cancer. In cross-sectional cohort study, we compared prevalence in PWH on stable antiretroviral therapy overweight individuals age- sex-matched population controls. The adjusted age was...
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 HIV infection and antiretroviral therapy have been linked to mitochondrial dysfunction. The role of platelet dysfunction in thrombosis, immunoregulation age-related diseases is increasingly appreciated. Here, we studied DNA content (mtDNA pl ) function people living with (PLHIV) related this function. In a cohort 208 treated PLHIV 56 uninfected controls, mtDNA was quantified, as well activation, agonist-induced reactivity inflammation by circulating factors flow cytometry. subgroup...
Long-term changes in the immune system of successfully treated people living with HIV (PLHIV) remain incompletely understood. In this study, we assessed 108 white blood cell (WBC) populations a cohort 211 PLHIV on stable antiretroviral therapy and 56 HIV-uninfected controls using flow cytometry. We show that marked differences exist T maturation differentiation between controls: had reduced percentages CD4+ cells naïve increased CD8+ cells, effector helper 17 (Th17) together Th17/regulatory...
Introduction People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility omics technologies for application larger cohorts, we compared multiple data layers. Methods Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis ATAC-seq as well ex vivo drug stimulation were performed in a small number blood samples derived from...
Abstract Blood platelets can interact with bacteria, possibly leading to platelet activation, cytokine and microparticle release immune signalling. Besides, bacteria also affect the RNA content. We investigated impact of non-pathogenic K12 pathogenic O18:K1 Escherichia (E.) coli strains on expression patterns, selected proteins. Depending concentration, contact E. lead an increase P-selectin (24–51.3%), CD63 (15.9–24.3%), PAC-1 (3.8–14.9%) bound fibrinogen (22.4–39%) surface. did not these...
Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are associated with cardiovascular risk inflammation. In a previous cross-sectional study, individuals using raltegravir (RAL)-based regimen were found to have reduced platelet reactivity PMA compared other antiretroviral regimens. Our aim was investigate whether switching from nonintegrase inhibitor RAL-based reduces or PMA.An investigator initiated, single-centre, prospective randomized, open-label, blinded endpoint...
Background: D-dimer concentrations in people living with HIV (PLHIV) on combination antiretroviral therapy (cART) are increased and have been linked to mortality. is a biomarker of vivo coagulation. In contrast reports D-dimer, data coagulation capacity PLHIV conflicting. this study, we assessed the effect cART inflammation capacity. Setting: We explored using calibrated thrombin generation (TG) persistent cross-sectional study including viral suppression uninfected controls. Methods: used...
Abstract Previous studies have shown that monocytes can be ‘trained’ or tolerized by certain stimuli to respond stronger weaker a secondary stimulation. Rewiring of glucose metabolism was found important in inducing this phenotype. As we previously Borrelia burgdorferi (B. burgdorferi), the causative agent Lyme borreliosis (LB), alters monocytes, hypothesized may also induce long-term changes innate immune responses. We exposure B. decreased cytokine production response TLR4-ligand...
Systemic chronic inflammation and immune dysfunction are recognized as drivers of the development non-AIDS related comorbidities (NARCs) in people living with HIV (PLHIV). In order to lower risk NARCs, it is critical elucidate what contribution alterations composition function circulating cells NARCs-related pathogenesis. Findings from previous immunophenotyping studies PLHIV highly heterogeneous not fully understood extent phenotypic changes on play a role dysregulated inflammatory response...
Abstract Here we describe an adult female with severe fasciitis and skin necrosis who carried a private, predicted deleterious missense mutation in OTULIN heterozygozity. is cellular regulator of deubiquitination that has been shown to play key role intrinsic immunity against staphylococcal α-toxin. The patient was treated broad spectrum antibiotics multiple surgical explorations were conducted without clinical response. Since autoinflammation the predominant feature, TNF inhibition started...
Abstract C-C chemokine receptor 5 (CCR5) is the main HIV co-receptor affecting susceptibility and disease course. Quantitative trait loci (QTL) mapping analysis was performed to assess genetic variants associated with CCR5 expression on circulating immune cells in 209 PLHIV using ART 304 healthy controls, all of Western European ancestry. The proportions positive mean fluorescence intensity (MFI) were assessed by flow cytometry monocytes CD4 + CD8 T cell subsets cytometry. We identified...