A5070177536- Parasites and Host Interactions
- Parasite Biology and Host Interactions
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Research on Leishmaniasis Studies
- Macrophage Migration Inhibitory Factor
- Helminth infection and control
- Immunotherapy and Immune Responses
- Asthma and respiratory diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Immune responses and vaccinations
- IL-33, ST2, and ILC Pathways
- Allergic Rhinitis and Sensitization
- Immune Response and Inflammation
- Metabolism, Diabetes, and Cancer
- Vitamin D Research Studies
- Complement system in diseases
- Child Nutrition and Water Access
- Invertebrate Immune Response Mechanisms
- Malaria Research and Control
- Cancer Immunotherapy and Biomarkers
- Mast cells and histamine
- Dermatology and Skin Diseases
- Genomics, phytochemicals, and oxidative stress
- Cholesterol and Lipid Metabolism
Leiden University Medical Center
2015-2024
Leiden University
2021
Loyola University Medical Center
2015
Chronic low-grade inflammation associated with obesity contributes to insulin resistance and type 2 diabetes. Helminth parasites are the strongest natural inducers of immune responses, short-lived infection rodent nematodes was reported improve glucose tolerance in obese mice. Here, we investigated effects chronic (12 weeks) Schistosoma mansoni, a helminth that infects millions humans worldwide, on whole-body metabolic homeostasis white adipose tissue (WAT) cell composition high-fat...
Chronic helminth infections, such as schistosomes, are negatively associated with allergic disorders. Here, using B cell IL-10-deficient mice, Schistosoma mansoni-mediated protection against experimental ovalbumin-induced airway inflammation (AAI) was shown to be specifically dependent on IL-10-producing cells. To study the organs involved, we transferred cells from lungs, mesenteric lymph nodes or spleen of OVA-infected mice recipient OVA-sensitized and showed that both lung splenic reduced...
Infection with the helminth Schistosoma (S.) mansoni drives development of interleukin (IL)-10-producing regulatory B (Breg) cells in mice and man, which have capacity to reduce experimental allergic airway inflammation are thus high therapeutic interest. However, both involved antigen cellular mechanisms that drive Breg cell remain be elucidated. Therefore, we investigated whether S. soluble egg antigens (SEA) directly interact enhance their potential, or act indirectly on via SEA-modulated...
Summary Background Regulatory B cells have been identified that strongly reduce allergic and auto‐immune inflammation in experimental models by producing IL ‐10. Recently, several human regulatory B‐cell subsets with an impaired function auto‐immunity described, but there is no information on asthma. Objective In this study, the frequency of ‐10 asthma were investigated. Methods Isolated peripheral blood from 13 patients matched healthy controls analyzed for expression different markers....
Background. Chronic schistosome infections are associated with T-cell hyporesponsiveness and a strong regulatory network. Murine studies have shown that can induce CD1dhi B cells, which inhibit inflammatory responses. Here, we evaluated the influence of cells (Bregs) on cytokines in vitro human schistosomiasis. Methods. Gabonese young adults were recruited from areas where Schistosoma haematobium (S.h) high or low endemic. The study participants categorized as infected uninfected an endemic...
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...
Type 2 immunity plays an essential role in the maintenance of metabolic homeostasis and its disruption during obesity promotes meta-inflammation insulin resistance. Infection with helminth parasite Schistosoma mansoni treatment soluble egg antigens (SEA) induce a type immune response organs improve sensitivity glucose tolerance obese mice, yet, causal relationship remains unproven. Here, we investigated effects underlying mechanisms T2 ribonuclease omega-1 (ω1), one major S immunomodulatory...
It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-β nitric oxide (NO). We hypothesized that adjuvant Cholera Toxin subunit (CTB) could imprint non-mucosal DCs to induce...
A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome exposure. Recently, we established CHI-S using single-sex male-only Schistosoma mansoni (Sm) cercariae in Schistosoma-naïve individuals. Given important differences antigenic profile to schistosomes of different sex, pioneered a female-only future use development.We exposed 13 healthy, adult participants 10 (n = 3) or 20 10)...
To accelerate the development of novel vaccines for schistosomiasis, we set out to develop a human model Schistosoma mansoni infection in healthy volunteers. During natural infections, female schistosomes produce eggs that give rise morbidity. Therefore, produced single-sex, male cercariae without egg production and associated pathology. Cercariae were their intermediate snail hosts accordance with principles good manufacturing practice (GMP). The application GMP an unconventional process is...
Obesity-associated metabolic inflammation drives the development of insulin resistance and type 2 diabetes, notably through modulating innate adaptive immune cells in organs. The nutrient sensor liver kinase B1 (LKB1) has recently been shown to control cellular metabolism T cell priming functions DCs. Here, we report that hepatic DCs from high-fat diet–fed (HFD-fed) obese mice display increased LKB1 phosphorylation deficiency (CD11cΔLKB1) worsened HFD-driven steatosis impaired glucose...
Summary Chronic helminth infection with Schistosoma (S.) mansoni protects against allergic airway inflammation ( AAI ) in mice and is associated reduced Th2 responses to inhaled allergens humans, despite the presence of schistosome‐specific immunity. Schistosome eggs strongly induce type 2 immunity allow study dynamics versus regulatory absence worms. Treatment isolated S. by i.p. injection prior induction ovalbumin OVA )/alum led significantly as assessed less BAL lung eosinophilia,...
B-cells play a critical role in the formation of immune responses against pathogens by acting as antigen-presenting cells, modulating and generating memory antibody responses. Here, we studied B-cell subset distributions between regions with higher lower microbial exposure, i.e. comparing peripheral blood from people living Indonesia or Ghana to those healthy Dutch residents using 36-marker mass cytometry panel. By applying an unbiased multidimensional approach, observed differences balance...
In humans and murine models of malaria, intradermal immunization (ID-I) with genetically attenuated sporozoites that arrest in liver induces lower protective immunity than intravenous (IV-I). It is unclear whether this difference caused by fewer migrating into the or suboptimal hepatic injection site-dependent immune responses. We therefore developed a Plasmodium yoelii immunization/boost/challenge model to examine parasite loads as well lymph node responses protected unprotected ID-I IV-I...
Chronic infection with Schistosoma mansoni parasites is associated reduced allergic sensitization in humans, while schistosome eggs protects against airway inflammation (AAI) mice. One of the main secretory/excretory molecules from glycosylated T2-RNAse Omega-1 (ω1). We hypothesized that ω1 induces protection AAI during infection. Peritoneal administration prior to Ovalbumin (OVA) eosinophilia and pathology, OVA-specific Th2 responses upon challenge, independent changes regulatory T cells....
The helminth Schistosoma mansoni (S. mansoni) induces a network of regulatory immune cells, including interleukin (IL)-10-producing B cells (Bregs). However, the signals required for development and activation Bregs are not well characterized. Recent reports suggest that helminths induce type I interferons (IFN-I), IFN-I drive in humans. We therefore assessed role induction by S. mansoni. Mice chronically infected with or i.v. injected soluble egg antigen (SEA) developed systemic signature....
During chronic schistosome infections, a complex regulatory network is induced to regulate the host immune system, in which IL-10-producing B (Breg) cells play significant role. Schistosoma mansoni soluble egg antigens (SEA) are bound and internalized by induce both human mouse IL-10 producing Breg cells. To identify Breg-inducing proteins SEA, we fractionated SEA size exclusion chromatography found 6 fractions able production (out of 18) high, medium low molecular weight (MW) range. The...
Assays which enable the detection of schistosome gut-associated circulating anodic (CAA) and cathodic (CCA) antigen in serum or urine are increasingly used as a diagnostic tool for infection. However, little is known about production clearance these antigens relation to sex reproductive maturity parasite. Here we describe CAA CCA excretion patterns by exploring mouse model after exposure 36 male-only, female-only mixed (male/female) Schistosoma mansoni cercariae. We found that levels,...
Abstract Type 2 immunity plays an essential role in the maintenance of metabolic homeostasis and its disruption during obesity promotes meta-inflammation insulin resistance. Infection with helminth parasite Schistosoma mansoni treatment soluble egg antigens (SEA) can induce a type immune response organs improve sensitivity glucose tolerance obese mice, yet causal relationship remains unproven. Here, we investigated effects underlying mechanisms T2 ribonuclease omega-1 (ω1), one major S....
How mechanistic target of rapamycin complex 1 (mTORC1), a key regulator cellular metabolism, affects dendritic cell (DC) metabolism and T cell-priming capacity has primarily been investigated in vitro, but how mTORC1 regulates this vivo remains poorly defined. Here, using mice deficient for component raptor DCs, we find that loss negatively glycolytic fatty acid maturation conventional particularly cDC1s. Nonetheless, antigen-specific CD8+ responses to infection are not compromised even...
Abstract Dendritic cells (DCs) play a crucial role in promoting tolerance through priming of regulatory T (Treg). Several studies indicate DC tolerogenicity is dependent on catabolic metabolism. However, the AMP-activated Kinase (AMPK), key energy and nutrient sensor driving metabolism, this process unclear. We found that human retinoic acid-induced tolerogenic CD103 + DCs (RA-DCs) display increased AMPK signaling. Interestingly, RA-DCs, but not vitamin-D3- or dexamethasone-induced DCs,...