- Pneumonia and Respiratory Infections
- Bacterial Infections and Vaccines
- Immune Response and Inflammation
- Respiratory viral infections research
- Genetic Associations and Epidemiology
- Influenza Virus Research Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Infective Endocarditis Diagnosis and Management
- Streptococcal Infections and Treatments
- Gut microbiota and health
- Immune Cell Function and Interaction
- Complement system in diseases
- Sodium Intake and Health
- Salmonella and Campylobacter epidemiology
- Diet and metabolism studies
- Sepsis Diagnosis and Treatment
- Listeria monocytogenes in Food Safety
- SARS-CoV-2 and COVID-19 Research
- Genomics and Phylogenetic Studies
- Immunodeficiency and Autoimmune Disorders
- Pediatric health and respiratory diseases
- Nosocomial Infections in ICU
- Lysosomal Storage Disorders Research
- Malaria Research and Control
- Genetic diversity and population structure
University of Amsterdam
2016-2024
Amsterdam University Medical Centers
2019-2024
Amsterdam University College
2024
Amsterdam Neuroscience
2017-2021
Academic Medical Center
2016-2018
University of Pennsylvania
2011-2012
Radboud University Medical Center
2009-2012
Radboud University Nijmegen
2007-2012
University Medical Center Utrecht
2009
Eijkman Institute for Molecular Biology
2009
Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family which four women were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X beta-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate binding, and led to defective production cytokines (interleukin-17, tumor necrosis factor, interleukin-6) after stimulation with Candida...
Infectious diseases exert a constant evolutionary pressure on the genetic makeup of our innate immune system. Polymorphisms in Toll-like receptor 4 (TLR4) have been related to susceptibility Gram-negative infections and septic shock. Here we show that two polymorphisms TLR4, Asp299Gly Thr399Ile, unique distributions populations from Africa, Asia, Europe. Genetic functional studies are compatible with model which nonsynonymous polymorphism has evolved as protective allele against malaria,...
Background. Intensive treatment of hematological malignancies with hematopoietic stem cell transplantation (HSCT) is accompanied by a high incidence opportunistic invasive fungal infection, but individual risk varies significantly. Dectin-1, C-type lectin that recognizes 1,3-β-glucans from pathogens, including Candida species, involved in the initiation immune response against fungi. Methods. Screening for DECTIN-1 Y238X polymorphism within group 142 patients undergoing HSCT was correlated...
African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation tropical environment. Here, we analyze Illumina 1M SNP array data in three Western populations from Cameroon and neighboring Bantu-speaking agricultural with whom they have admixed. We infer genome-wide ancestry, scan for signals positive selection, perform targeted genetic association measured height variation. identify multiple regions throughout the...
ObjectivesListeria monocytogenes is a food-borne pathogen that can cause meningitis. The listerial genotype ST6 has been linked to increasing rates of unfavourable outcome over time. We investigated genetic variation and the relation with clinical in meningitis.MethodsWe sequenced 96 isolates from adults meningitis included two prospective nationwide cohort studies by whole genome sequencing, evaluated associations between bacterial outcome. validated these results screening genotypes 445...
Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host pathogen known to play role in pneumococcal disease, though what extent unknown. In genome-wide association study human we show that explains almost half susceptibility meningitis one-third severity, identifying variants CCDC33 associated with susceptibility. Pneumococcal genetic large amount potential...
Abstract Aims Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVDs). The composition abundance of gut trophic networks differ between ethnicities. We aim evaluate the relationship microbiotal CVD phenotypes. Methods results included cross-sectional data from 3860 individuals without history 6 ethnicities living in Amsterdam region participating prospective Healthy Life Urban Setting (HELIUS) study. Genetic variants were genotyped, faecal profiled,...
Adequate responses by our innate immune system toward invading pathogens were of vital importance for surviving infections, especially before the antibiotic era. Recently, a polymorphism in Mal (Ser180Leu, TIRAP rs8177374), an important adaptor protein downstream Toll-like receptor (TLR) 2 and 4 pathways, has been described to provide protection against broad range infectious pathogens. We assessed functional effects this human experimental endotoxemia, we demonstrate that individuals...
A deficiency in ADAMTS13 (a von Willebrand factor [VWF] cleaving protease) is associated with accumulation of prothrombogenic unusually large VWF multimers (UL-VWF) plasma. We studied release and proteolysis patients symptomatic Plasmodium falciparum or P. vivax malaria on the Indonesian island Sumba. Malaria had significantly lower platelet counts higher concentrations activation factors than healthy hospital staff controls. The latter indicates that a amount circulating was conformation...
It has been proposed that individual genetic variation contributes to the course of severe infections and sepsis. Recent studies single nucleotide polymorphisms (SNPs) within endotoxin receptor its signaling system showed an association with risk disease development. This study aims examine response associated variations TLR4, for bacterial LPS, a central intracellular signal transducer (TIRAP/Mal) on cytokine release susceptibility hospital acquired in distinct patient populations.Three...
Recent studies have provided evidence for rapid pathogen genome diversification, some of which could potentially affect the course disease. We previously described such variation seen between isolates infecting blood and cerebrospinal fluid (CSF) a single patient during case bacterial meningitis. Here, we performed whole-genome sequencing paired from CSF 869 meningitis patients to determine whether frequently occurs these two niches in cases Using combination reference-free variant calling...
Significance Pneumococcal meningitis, the most frequent cause of bacterial meningitis in adults, is associated with substantial morbidity and mortality. In a prospective, nationwide cohort patients pneumococcal macrophage migration inhibitory factor (MIF), proinflammatory mediator, was identified as previously unidentified genetic marker patient’s outcome. High-expression MIF alleles were disease severity death, finding consistent harmful consequences robust cytokine responses on brain edema...
Toll-like receptor 4 (TLR4) plays an important role in the pattern recognition of Mycobacterium tuberculosis, and polymorphisms TLR4 gene influence function receptor. We therefore investigated a cohort HIV-infected Tanzanian patients whether Asp299Gly polymorphism is associated with development active tuberculosis. found greater risk developing tuberculosis as well reduction CD4 T-cell counts polymorphism.
ABSTRACT Upon the invasion of host by microorganisms, innate immunity is triggered through pathogen recognition pattern receptors (PRRs). Toll-like (TLRs) are best-studied class PRRs, and they recognize specific pathogen-associated molecular patterns (PAMPs) from various microorganisms. A large number studies have shown that genetic variation in TLRs may influence susceptibility to infections. We assessed TLR2 , which encodes one most important TLRs, populations around globe correlated it...
Abstract Population genetic structure is determined both by current processes and historical events. Current include gene flow, which largely influenced the migration capacity of a species. Historical events are, for example, glaciation periods, have had major impact on distribution many Species with low or tendency to move about disperse often exhibit clear spatial structures, whereas mobile species mostly show less differentiation. In this paper we report small, wingless arthropod (...
The occurrence of oropharyngeal candidiasis (OPC) in combination with HIV disease progression is a very common phenomenon. However, not all HIV-infected patients develop OPC, even when they progress to low CD4 T-cell counts. Because immunity defective AIDS, the innate defence mechanisms are likely have central role antifungal these patients. We investigated whether genetic variations immune genes DECTIN-1, TLR2, TLR4, TIRAP, and CASPASE-12 associated presence OPC subjects from East Africa.A...
Use of genetic risk scores (GRS) may help to distinguish between type 1 diabetes and 2 diabetes, but less is known about whether GRS are associated with disease severity or progression after diagnosis. Therefore, we tested residual beta cell function glycaemic control in individuals diabetes.
The vast majority of streptococci colonizing the human upper respiratory tract are commensals, only sporadically implicated in disease. Of these, most pathogenic is Mitis group member, Streptococcus pneumoniae . Phenotypic and genetic similarities between can cause difficulties species identification. Using ribosomal S2-gene sequences extracted from whole-genome published 501 streptococci, we developed a method to identify streptococcal species. We validated this on non-pneumococcal isolates...