A5019184331- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- Autophagy in Disease and Therapy
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Cell death mechanisms and regulation
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Tuberculosis Research and Epidemiology
- Vibrio bacteria research studies
- Viral gastroenteritis research and epidemiology
- Protease and Inhibitor Mechanisms
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Escherichia coli research studies
- T-cell and B-cell Immunology
- Liver Disease Diagnosis and Treatment
- Toxoplasma gondii Research Studies
- Aquaculture disease management and microbiota
- Lipid Membrane Structure and Behavior
- Gut microbiota and health
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Vector-borne infectious diseases
- Advanced Electron Microscopy Techniques and Applications
Kiel University
2021-2025
University of Oslo
2013-2024
Max Planck Institute of Molecular Cell Biology and Genetics
2019-2021
Jožef Stefan Institute
2007-2016
Leiden University
2008
Blood Transfusion Centre of Slovenia
2003-2007
Leiden University Medical Center
2006
University of Ljubljana
2000
Mycobacterium tuberculosis modulation of macrophage cell death is a well-documented phenomenon, but its role during bacterial replication less characterized. In this study, we investigate the impact plasma membrane (PM) integrity on in different functional populations human primary macrophages. We discovered that IFN-γ enhanced colony-stimulating factor–differentiated macrophages more than granulocyte–macrophage show permissiveness to growth result differential ability preserve PM integrity....
Continuing the study of physicochemical and biological properties ruthenium-quinolone adducts, four novel complexes with general formula [Ru([9]aneS3)(dmso-κS)(quinolonato-κ2O,O)](PF6), containing quinolones levofloxacin (1), nalidixic acid (2), oxolinic (3), cinoxacin (4), were prepared characterized in solid state as well solution. Contrary to their organoruthenium analogues, these are generally relatively stable aqueous solution substitution dimethylsulfoxide (dmso) ligand is slow not...
Egress of malaria parasites from the host cell requires concerted rupture its enveloping membranes. Hence, we investigated role plasmodial perforin-like protein PPLP2 in egress Plasmodium falciparum erythrocytes. is expressed blood stage schizonts and mature gametocytes. The localizes vesicular structures, which activated gametocytes discharge a calcium-dependent manner. comprises MACPF domain recombinant has haemolytic activities towards PPLP2-deficient [PPLP2(−)] merozoites show normal...
Oral exposure to nanomaterials is a current concern, asking for innovative biological test systems assess their safety, especially also in conditions of inflammatory disorders. Aim this study was develop 3D intestinal model, consisting Caco-2 cells and two human immune cell lines, suitable nanomaterial toxicity, either healthy or diseased conditions. Human macrophages (THP-1) dendritic (MUTZ-3) were embedded collagen scaffold seeded on the apical side transwell inserts. top layer, forming...
The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS) to form in phagocytes a distinct "Legionella-containing vacuole" (LCV), which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed presence small GTPase Ran its effector RanBP1 on purified LCVs. Here we validate that localize LCVs promote intracellular growth L. pneumophila. Moreover, pneumophila protein LegG1, contains putative RCC1 guanine nucleotide...
The enhanced permeability and retention (EPR) effect is the only described mechanism enabling nanoparticles (NPs) flowing in blood to reach tumors by a passive targeting mechanism. Here, using transparent zebrafish model infected with Mycobacterium marinum we show that an EPR-like process also occurs allowing different types of NPs extravasate from vasculature granulomas assemble during tuberculosis (TB) infection. PEGylated liposomes other NP cross endothelial barriers near infection sites...
The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. host pathways mechanisms that contribute maintaining Mtb phagosome integrity have not been investigated. Here, we examined spatiotemporal dynamics of Mtb-containing identified an interferon-gamma-stimulated Rab20-dependent membrane trafficking pathway in macrophages maintains spacious proteolytic phagolysosomes. This functions promote endosomal influx...
In extrapulmonary tuberculosis, the most common site of infection is within lymphatic system, and there growing recognition that endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line vessels, as a niche for Mycobacterium tuberculosis lymph nodes patients with tuberculosis. cultured primary human LECs (hLECs), determined M. replicates both cytosol autophagosomes, but bacteria failed to replicate when virulence locus RD1 was deleted. Activation by IFN-γ...
L-leucyl-L-leucine methyl ester (LLOMe) induces apoptosis, which is thought to be mediated by release of lysosomal cysteine cathepsins from permeabilized lysosomes into the cytosol. Here, we demonstrated in HeLa cells that apoptotic as well sub-apoptotic concentrations LLOMe caused rapid and complete membrane permeabilization (LMP), evidenced loss proton gradient cytosol internalized markers below a relative molecular mass 10,000. However, there was no evidence for B L cytosol; rather they...
Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer surface of virulent members Mycobacterium tuberculosis (Mtb) complex, are a major contributing factor to pathogenesis Mtb. Myelocytic cells, such as macrophages and dendritic primary hosts for Mtb after infection previous studies have shown multiple roles PDIM in supporting these cells. However, can infect other cell types. We previously showed that efficiently replicates human lymphatic endothelial cells (hLECs) hLEC cytosol...
Effector molecules translocated by the Salmonella pathogenicity island (SPI)1-encoded type 3 secretion system (T3SS) critically contribute to pathogenesis of human infection. They facilitate internalization non-phagocytic enterocytes rendering intestinal epithelium an entry site for Their function in vivo has remained ill-defined due lack a suitable animal model that allows visualization intraepithelial Salmonella. Here, we took advantage our novel neonatal mouse and analyzed various...
Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases localized in the nucleus and cytosol. Loss-of-function mutations stefin gene (CSTB) were reported patients with Unverricht-Lundborg disease (EPM1). We have identified interaction between nucleosomes, specifically histones H2A.Z, H2B, H3. In synchronized T98G cells, co-immunoprecipitated histone H3, predominantly G(1) phase cell cycle. B-deficient mouse embryonic fibroblasts entered S earlier than wild type fibroblasts....
The vacuolar H(+)-ATPase (v-ATPase) complex is instrumental in establishing and maintaining acidification of some cellular compartments, thereby ensuring their functionality. Recently it has been proposed that the transmembrane V0 sector v-ATPase its a-subunits promote membrane fusion endocytic exocytic pathways independent functions. Here, we tested if such a proton-pumping role also applies to phagosome-lysosome fusion. Surprisingly, endo(lyso)somes mouse embryonic fibroblasts lacking a3...
Cysteine cathepsins are primarily lysosomal proteases involved in general protein turnover, but they also have specific proteolytic functions antigen presentation and bone remodeling. Cathepsins most stable at acidic pH, although growing evidence indicates that physiologically relevant activity neutral pH. Post-translational processing of mature chemokines is a key, yet underappreciated, level chemokine regulation. Although the role selected serine matrix metalloproteases has long been...
Vaccine development against extracellular bacteria has been important for the sustainability of aquaculture industry. In contrast, infections with intracellular pathogens remain largely an unresolved problem. Francisella noatunensis subsp. orientalis is a Gram-negative, facultative bacterium that causes disease francisellosis in fish. Francisellosis commonly characterized as chronic granulomatous high morbidity and can result mortality depending on host. this study, we explored potential...
Abstract Many cellular organelles, including endosomes, show compartmentalization into distinct functional domains, which, however, cannot be resolved by diffraction‐limited light microscopy. Single molecule localization microscopy (SMLM) offers nanoscale resolution but data interpretation is often inconclusive when the ultrastructural context missing. Correlative electron (CLEM) combining SMLM with (EM) enables correlation of subdomains organelles in relation to their underlying...