A5060321719- Malaria Research and Control
- Mosquito-borne diseases and control
- Parasites and Host Interactions
- Click Chemistry and Applications
- Nanoplatforms for cancer theranostics
- Prostate Cancer Diagnosis and Treatment
- Cancer Research and Treatments
- Invertebrate Immune Response Mechanisms
- Parasite Biology and Host Interactions
- Immunotherapy and Immune Responses
- Prostate Cancer Treatment and Research
- Urologic and reproductive health conditions
- Chemokine receptors and signaling
- Vector-borne infectious diseases
- Advancements in Transdermal Drug Delivery
- Research on Leishmaniasis Studies
- Sexual function and dysfunction studies
- Helminth infection and control
- Coccidia and coccidiosis research
- Extracellular vesicles in disease
- Leptospirosis research and findings
- Ultrasound and Hyperthermia Applications
- Macrophage Migration Inhibitory Factor
- Orthopedic Infections and Treatments
- Bacterial Infections and Vaccines
Leiden University Medical Center
2016-2024
Leiden University
2022-2023
ABSTRACT Helminths like Schistosoma mansoni release excretory/secretory (E/S) products that modulate host immunity to enable infection. Extracellular vesicles (EVs) are among these E/S products, yet molecular mechanisms and functionality of S. EV interaction with immune cells is unknown. Here we demonstrate EVs released by schistosomula internalised human monocyte‐derived dendritic (moDCs). Importantly, show this uptake was mainly mediated via DC‐SIGN (CD209). Blocking almost completely...
The potential of receptor-mediated fluorescence-based image-guided surgery tracers is generally linked to the near-infrared emission profile and good-manufacturing-production availability fluorescent dyes. Surprisingly, little known about critical interaction between structural composition dyes pharmacokinetics tracers. In this study, a dual-modality tracer design was used systematically quantitatively evaluate influence elongation polymethine chain in cyanine dye on imaging targeted tracer....
Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic (pGlu). Here, we report the biochemical and functional analysis Plasmodium QC. We show that sporozoites QC-null mutants rodent human malaria parasites are recognized by mosquito immune system melanized when they reach hemocoel. Detailed analyses showed sporozoite numbers in salivary glands reduced mosquitoes infected with QC catalytically dead mutants. This phenotype...
Following initial invasion of Schistosoma mansoni cercariae, schistosomula reside in the skin for several days during which they can interact with dermal immune system. While murine experiments have indicated that exposure to radiation-attenuated (RA) cercariae generate protective immunity is initiated stage, contrasting non-attenuated such data missing human model. Since does not form a reliable marker responses skin, we used explants study interaction and RA innate antigen presenting cells...
There is a need to develop diagnostic and analytical tools that allow noninvasive monitoring of bacterial growth dissemination in vivo. For such cell-tracking studies hold translational value controlled human infections, which volunteers are experimentally colonized, they should not require genetic modification, tracking over number replication cycles. To gauge if an antimicrobial peptide tracer, 99mTc-UBI29–41-Cy5, contains both fluorescent radioactive moiety, could be used for vivo...
Professional antigen-presenting cells (APCs), like macrophages (Mϕs) and dendritic (DCs), are central players in the induction of natural vaccine-induced immunity to malaria, yet very little is known about interaction SPZ with human APCs. Intradermal delivery whole-sporozoite vaccines reduces their effectivity, possibly due dermal immunoregulatory effects. Therefore, understanding these interactions could prove pivotal malaria vaccination. We investigated APC responses recombinant...
Given the number of global malaria cases and deaths, need for a vaccine against Plasmodium falciparum (Pf) remains pressing. Administration live, radiation-attenuated Pf sporozoites can fully protect malaria-naïve individuals. Despite fact that motility these attenuated parasites is key to their infectivity ultimately protective efficacy, sporozoite in human tissue (e.g. skin) wholly uncharacterized date. We show ability quantitatively address complexity provides an additional tool...
Abstract Background Sporozoites (SPZ), the infective form of Plasmodium falciparum malaria, can be inoculated into human host skin by Anopheline mosquitoes. These SPZ migrate at approximately 1 µm/s to find a blood vessel and travel liver where they infect hepatocytes multiply. In are still low in number (50–100 SPZ) vulnerable immune attack antibodies macrophages. This is why whole proteins used as basis for most malaria vaccines currently deployed undergoing late clinical testing....
Introduction: The skin stage of malaria is a vital and vulnerable migratory life the parasite. It has been characterised in rodent models, but remains wholly uninvestigated for human parasites. To enable depth analysis not genetically modified (non-GMO) Plasmodium falciparum (Pf) sporozoite behaviour skin, we devised labelling technology (Cy5M2, targeting mitochondrion) that supports tracking individual non-GMO sporozoites skin. Methods: Sporozoite with Cy5M2 was performed vitro as well via...
The protective efficacy of the most promising malaria whole-parasite based vaccine candidates critically depends on parasite's potential to migrate in human host. Key components parasite motility machinery (e.g. adhesive proteins, actin/myosin-based motor, geometrical properties) have been identified, however regulation this is an unknown process.In vitro microscopic live imaging parasites different formulations was performed and analysed, with quantitative analysis software SMOOTIn vitro,...
Hybrid tracers containing both fluorescent and radioactive imaging labels have demonstrated clinical potential during sentinel lymph node procedures. To combine these two on a single targeting vector that allows tumor-targeted imaging, end-labeling strategies are often applied. For αvβ3-integrin-targeting hybrid tracers, providing an excellent model for evaluating tracer development strategies, end-labeling-based synthesis provides rather cumbersome strategy. Hence, the aim of this study was...
Abstract Emerging evidence suggests that immune cells not only communicate with each other through cytokines, chemokines, and cell surface receptors, but also by releasing small membranous structures known as extracellular vesicles (EVs). EVs carry a variety of different molecules can be taken up recipient cells. Parasitic worms are well for their immunomodulatory properties, whether they affect responses altering EV‐driven communication between host remains unclear. Here we provide...
Background The parasitic trematode Fasciola hepatica evades host immune defenses through secretion of various immunomodulatory molecules. Fatty Acid Binding Proteins ( fh FABPs) are among the main excreted/secreted proteins and have been shown to display anti-inflammatory properties. However, little is currently known regarding their impact on dendritic cells (DCs) subsequent capacity prime specific CD4 + T cell subsets. Methodology/Principal Findings effects both native F. extracts...
The availability of a receptor for theranostic pretargeting approaches was assessed by use new click-chemistry-based deactivatable fluorescence-quenching concept. efficacy evaluated in cell-based model system featuring both membranous (available) and internalized (unavailable) fractions the clinically relevant chemokine 4 (CXCR4). Proof concept achieved with tracer consisting CXCR4-specific peptide functionalized Cy5 dye bearing chemoselective azide handle (N
Malaria vaccine candidates based on live, attenuated sporozoites have led to high levels of protection. However, their efficacy critically depends the sporozoites' ability reach and infect host liver. Administration via mosquito inoculation is by far most potent method for inducing immunity but highly impractical. Here, we observed that intradermal syringe-injected Plasmodium berghei (syrSPZ) were 3-fold less efficient in migrating infecting mouse liver than mosquito-inoculated (msqSPZ)....
Abstract Antibodies can prevent malaria by neutralizing the infectious Plasmodium falciparum sporozoites (SPZ) before they establish an infection in liver. Circumsporozoite protein (CSP), most abundant surface of SPZ is leading candidate for passive (and subunit) immunization approaches against malaria. Comprehensive assessment parasite-inhibitory capacity anti-CSP monoclonal antibodies (mAbs) important step advancing CSP-based strategies. In this study, we employed a quantitative...
In an era of antimicrobial resistance, a better understanding the interaction between bacteria and sentinel immune system is needed to discover new therapeutic targets for combating bacterial infectious disease. Sentinel cells such as macrophages phagocytose intact thereby initiate ensuing responses. The surface composition key element that determines macrophage signaling. To study role cell in recognition, we developed platform technology altering surfaces controlled manner with versatile...
Liver cancer is a leading cause of deaths worldwide. Surgical resection superficial hepatic lesions increasingly guided by the disrupted bile excretion fluorescent dye indocyanine green (ICG). To extend this approach to deeper lesions, dedicated bimodal tracer that facilitates both fluorescence guidance and radioguidance was developed.
Abstract Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic (pGlu). Here, we report the biochemical and functional analysis Plasmodium QC. We show that sporozoites QC-null mutants are recognized by mosquito immune system melanized when they reach hemocoel. Sporozoite numbers in salivary glands also reduced mosquitoes infected with QC catalytically-dead mutants. This phenotype can be rescued genetic complementation...