A5035542829- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Aquaculture disease management and microbiota
- Zebrafish Biomedical Research Applications
- Immune Response and Inflammation
- Antibiotic Resistance in Bacteria
- interferon and immune responses
- Invertebrate Immune Response Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Barrier Structure and Function Studies
- Immune cells in cancer
- Bacterial Genetics and Biotechnology
- Neonatal and fetal brain pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immunodeficiency and Autoimmune Disorders
- Vibrio bacteria research studies
- Insect Utilization and Effects
- Genomics and Phylogenetic Studies
- Signaling Pathways in Disease
- Phagocytosis and Immune Regulation
- Protein Tyrosine Phosphatases
- Beetle Biology and Toxicology Studies
- Galectins and Cancer Biology
- Metabolomics and Mass Spectrometry Studies
- Cancer-related molecular mechanisms research
Amsterdam University Medical Centers
2018-2021
Amsterdam UMC Location Vrije Universiteit Amsterdam
2009-2020
Vrije Universiteit Amsterdam
2003-2020
Amsterdam UMC Location University of Amsterdam
2011-2012
University Medical Center
2012
University Hospital and Clinics
2012
Biology of Infection
2009
Hubrecht Institute for Developmental Biology and Stem Cell Research
2002
Zebrafish (Danio rerio) embryos are increasingly used as a model for studying the function of vertebrate innate immune system in host-pathogen interactions 1. The major cell types system, macrophages and neutrophils, develop during first days embryogenesis prior to maturation lymphocytes that required adaptive responses. ease obtaining large numbers embryos, their accessibility due external development, optical transparency embryonic larval stages, wide range genetic tools, extensive mutant...
Streptococcus pneumoniae is one of the most important causes bacterial meningitis, an infection where unfavourable outcome driven by and host-derived toxins. In this study, we developed characterized a pneumococcal meningitis model in zebrafish embryos that allows for real-time investigation early host-microbe interaction.Zebrafish were infected caudal vein or hindbrain ventricle with green fluorescent wild-type S. D39 pneumolysin-deficient mutant. The kdrl:mCherry transgenic line was used...
Bacterial virulence is best studied in animal models. However, the lack of possibilities for real time analysis and need laborious invasive sample limit use experimental animals. In present study 28 h-old zebrafish embryos were infected with DsRed-labelled cells Salmonella typhimurium. Using multidimensional digital imaging microscopy we able to determine exact location fate these bacterial pathogens a living vertebrate host during three days. A low dose wild-type S. typhimurium resulted...
Innate immunity signaling mechanisms during vertebrate embryogenesis are largely unknown. To study Toll-like receptor (TLR) function in the zebrafish embryo model, we designed an experimental setup for antisense morpholino knockdown under conditions of bacterial infection. Clearance Salmonella enterica serovar Typhimurium Ra bacteria was significantly impaired after myeloid differentiation factor 88 (MyD88), a common adaptor protein TLR and interleukin-1 signaling. Thereby, demonstrate first...
Pathogenic mycobacteria have the ability to persist in phagocytic cells and suppress immune system. The glycolipid lipoarabinomannan (LAM), particular its mannose cap, has been shown inhibit phagolysosome fusion induce immunosuppressive IL-10 production via interaction with receptor or DC-SIGN. Hence, current paradigm is that cap of LAM a crucial factor mycobacterial virulence. However, above studies were performed purified LAM, never live bacteria. Here we evaluate biological properties...
During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis leprosy. To understand basis mycobacterial pathogenicity, it is crucial to identify molecular virulence mechanisms. In this study, we address contribution ESX-1 ESX-5--two homologous type VII secretion systems that secrete distinct sets immune modulators--during macrophage cycle. Using wild-type, ESX-1- ESX-5-deficient strains, demonstrate these differentially...
Abstract The recruitment of leukocytes to infectious foci depends strongly on the local release chemoattractant mediators. human CXC chemokine receptor 3 (CXCR3) is an important node in signaling network and expressed by multiple leukocyte lineages, including T cells macrophages. ligands this originate from ancestral CXCL11 gene early vertebrates. Here, we used optically accessible zebrafish embryo model explore function CXCR3-CXCL11 axis macrophage show that disruption increases resistance...
ABSTRACT Mycobacterium marinum causes a systemic tuberculosis-like disease in large number of poikilothermic animals and is used as model for mycobacterial pathogenesis. In the present study, we infected zebra fish ( Danio rerio ) with different strains M. to determine variation pathogenicity. Depending on isolate, developed an acute or chronic disease. Acute was characterized by uncontrolled growth pathogen death all within 16 days, whereas granuloma formation organs survival at least 4 8...
The zebrafish genome contains ten genes that encode class II cytokine-like peptides, of which the two are related most closely to mammalian interferon gamma (IFN-gamma) were named IFN-gamma1 and IFN-gamma2. Although has become a popular model system study immune mechanisms, although interferons central regulators immunity, cytokines correspond functionally IFN-gamma not been established. We used embryos assay functions IFN-gamma2, have identified subset homologs IFN-responsive as targets in...
SUMMARY The hallmark of tuberculosis (TB) is the formation granulomas, which are clusters infected macrophages surrounded by additional macrophages, neutrophils and lymphocytes. Although it has long been thought that granulomas beneficial for host, there evidence mycobacteria also promote these structures. In this study, we aimed to identify new mycobacterial factors involved in initial stages granuloma formation. We exploited zebrafish embryo Mycobacterium marinum infection model study...
Adaptive immunity in homeotherms depends greatly on CD4+ Th cells which release cytokines response to specific antigen stimulation. Whilst bony fish and poikilothermic tetrapods possess that express TcR CD4-related genes (that exist two forms teleost fish; termed CD4-1 CD4-2), date there is no unequivocal demonstration equivalent exist. Thus, this study we determined whether CD4-1+ lymphocytes can typical of following stimulation, using the zebrafish (Danio rerio). Initially, analyzed CD4...
ABSTRACT The interaction of environmental bacteria with unicellular eukaryotes is generally considered a major driving force for the evolution intracellular pathogens, allowing them to survive and replicate in phagocytic cells vertebrate hosts. To test this hypothesis on genome-wide level, we determined pathogen Mycobacterium marinum whether it uses conserved strategies exploit host from both protozoan origin. Using transposon-directed insertion site sequencing (TraDIS), differences genetic...
Next to the two-component and quorum sensing systems, cell-surface signaling (CSS) has been recently identified as an important regulatory system in Pseudomonas aeruginosa. CSS systems sense signals from outside cell transmit them into cytoplasm. They generally consist of a TonB-dependent outer membrane receptor, sigma factor regulator (or anti-sigma factor) cytoplasmic membrane, extracytoplasmic function (ECF) factor. Upon perception extracellular signal by receptor ECF is activated...
ESX-5 is a mycobacterial type VII protein secretion system responsible for transport of numerous PE and PPE proteins. It involved in the induction host cell death modulation cytokine response vitro. In this work, we studied effects embryonic adult zebrafish using Mycobacterium marinum. We found that ESX-5-deficient M. marinum was slightly attenuated embryos. Surprisingly, same mutant showed highly increased virulence zebrafish, characterized by bacterial loads early onset granuloma formation...
Galectin-4 (Gal-4) is a member of the galectin family glycan binding proteins that shows significantly higher expression in cystic tumors human pancreas and pancreatic adenocarcinomas compared to normal pancreas. However, putative function Gal-4 tumor progression cancer still incompletely understood. In this study role was investigated, using set defined cell lines, Pa-Tu-8988S (PaTu-S) Pa-Tu-8988T (PaTu-T), as model. These two lines are derived from same liver metastasis primary...
The pathogenicity of mycobacteria is closely associated with their ability to export virulence factors. For this purpose, possess different protein secretion systems, including the accessory Sec translocation pathway, SecA2. Although pathway intracellular survival and virulence, SecA2-dependent effector proteins remain largely undefined. In work, we studied a Mycobacterium marinum secA2 mutant an impaired capacity initiate granuloma formation in zebrafish embryos. By comparing proteomic...
Central nervous system (CNS) infection by Mycobacterium tuberculosis is one of the most devastating complications tuberculosis, in particular early childhood. In order to induce CNS infection, M. needs cross specialised barriers protecting brain. How crosses blood–brain barrier (BBB) and enters not well understood. Here, we use transparent zebrafish larvae closely related pathogen marinum answer this question. We show that stages development, mycobacteria rapidly infect brain tissue, either...