A5014853193- Parasitic Diseases Research and Treatment
- Parasites and Host Interactions
- Parasite Biology and Host Interactions
- Parasitic Infections and Diagnostics
- Insects and Parasite Interactions
- Insect symbiosis and bacterial influences
- Coccidia and coccidiosis research
- IL-33, ST2, and ILC Pathways
- T-cell and B-cell Immunology
- Helminth infection and control
- Monoclonal and Polyclonal Antibodies Research
- Protist diversity and phylogeny
- Eosinophilic Esophagitis
- Trypanosoma species research and implications
- Food Allergy and Anaphylaxis Research
- Malaria Research and Control
- Immune Cell Function and Interaction
- Biochemical Analysis and Sensing Techniques
- Mosquito-borne diseases and control
- Eosinophilic Disorders and Syndromes
- Toxoplasma gondii Research Studies
- TGF-β signaling in diseases
- Invertebrate Immune Response Mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Physiological and biochemical adaptations
University of Glasgow
2016-2024
Wellcome Centre for Molecular Parasitology
2016-2024
Wellcome Trust
2016-2018
Centre for Immunity, Infection and Evolution
2016
University of Edinburgh
1997-2016
Imperial College London
1984-1995
Leiden University
1993
University College London
1993
Thomas Jefferson University
1993
The Royal Free Hospital
1993
Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans animals, decimate crop production are a major impediment to socioeconomic development. Here we report broad comparative study 81 genomes parasitic non-parasitic worms. We have identified gene family births hundreds expanded families at key nodes in the phylogeny that relevant parasitism. Examples include modulate host immune responses, enable parasite migration though tissues or...
Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during lamina propria innate lymphoid (ILC2s) produce IL-13. This causes epithelial remodeling, including cell hyperplasia, the function of is unknown. We identified cholinergic effector cells, are only that expressed choline acetyltransferase (ChAT). During parasite mice with epithelial-specific deletion ChAT had increased worm burden, fitness, and...
The cytokine microenvironment is thought to play an important role in the generation of immunoregulatory cells. Nematode infections are commonly associated with Th2 cytokines and hyporesponsive T Here we show that IL-4-dependent macrophages recruited vivo by nematode parasite Brugia malayi actively suppress proliferation lymphocytes on co-culture vitro. These alternatively activated block cell-to-cell contact, implicating a receptor-mediated mechanism. Further, proliferative reversible not...
Abstract A population of 164 adult individuals resident in an area endemic for Brugia malayi lymphatic filariasis has been studied humoral immune responses to filarial parasites. Antibody levels Ag extracted from worms were determined each the IgG subclasses, IgM and IgE. The dominant isotype antifilarial antibody was IgG4, which represented 88% total asymptomatic microfilaremics, most whom possessed 100 1000 micrograms/ml specific this subclass (geometric mean 762 micrograms/ml). Patients...
Summary The surface antigens of Toxocara canis infective larvae have been identified by radio‐iodination and compared with the excretory‐secretory (ES) products released in vitro. Common antigens, molecular weight 32 000 120 are found on larval surface, ES material culture supernatant following iodination living T. larvae. consist three closely migrating bands each these preparations. However, one prominent component, 400 000, is not surface. Additional molecules 55 70 present material, but...
ABSTRACT HpARI is an immunomodulatory protein secreted by the intestinal nematode Heligmosomoides polygyrus bakeri , which binds and blocks IL-33. Here, we find that H. genome contains three family members these have different effects on IL-33-dependent responses in vitro vivo with HpARI1+2 suppressing HpARI3 amplifying responses. All HpARIs sub-nanomolar affinity for mouse IL-33; however, does not block IL-33-ST2 interactions. Instead, stabilizes IL-33, increasing half-life of cytokine to...
Natural infection with filarial nematode parasites shows many characteristics of a Th2 immune response. In these infections, long-lived adult worms inhabit the lymphatics, releasing laval microfilariae (Mf) into blood stream. To compare effect different developmental stages on mammalian system, Mf and either sex were implanted BALB/c mice, in which they survive for at least 28 days. Serum Ab responses showed that whereas stimulated specific Abs all IgG subclasses, but little total IgE, only...
In an area in which brugian filariasis is endemic, when cytokine levels were analyzed as a function of clinical status comparing those who asymptomatic and amicrofilaremic with microfilaremic, it was found that both interferon (IFN)-γ interleukin (IL)-5 suppressed microfilariae carriers (P < .01 P .001, respectively), but IL-4 unabated. Age had significant effect on production groups. subjects, high young persons decreased age, whereas microfilaremic increased significantly age. Conversely,...
Journal Article T Cell Responsiveness Correlates Differentially with Antibody Isotype Levels in Clinical and Asymptomatic Filariasis Get access Maria Yazdanbakhsh, Yazdanbakhsh Reprints or correspondence: Dr. Dept. of Parasito1ogy, Leiden University, Wassenaarseweg 62, Postbus 9605, 2300 RC Leiden, Netherlands. Search for other works by this author on: Oxford Academic PubMed Google Scholar William A. Paxton, Paxton Yvonne C. M. Kruize, Kruize Erliyani Sartono, Sartono Agnes Kurniawan,...
The nematode parasite Toxocara canis is found in all dog populations and poses a poorly defined health hazard to humans. We have studied excretory-secretory antigen (ES) surface antigens of the infective larval stage which tissue-invasive mammalian hosts. Antigens were probed with panel eight monoclonal antibodies raised mice whole ES. Six reacted periodate-sensitive carbohydrate epitopes on ES molecules, remaining two (Tcn-3 Tcn-6) recognized either peptide or periodate-resistant sugar...
Macrophage migration inhibitory factor (MIF) is a key innate immune mediator with chemokine- and cytokine-like properties in the inflammatory pathway. While its actions on macrophages are well-studied, effects other cell types less understood. Here we report that MIF required for expansion of intestinal tuft cells during infection helminth Nippostrongylus brasiliensis. MIF-deficient mice show defective responses following infection, lacking epithelial hyperplasia or upregulation goblet...
Evasion of host immunity by Toxocara canis infective larvae is mediated the nematode surface coat, which shed in response to binding antibody molecules or effector cells. The major constituent coat TES-120 glycoprotein series. We have isolated a 730-bp cDNA from gene encoding apoprotein precursor TES-120. mRNA absent T. adults but hyperabundant larvae, making up approximately 10% total mRNA, and trans-spliced with 5' leader sequence SL1. It encodes 15.8-kDa protein (after signal peptide...
A cDNA expression library constructed from RNA derived adult stage Brugia pahangi (mixed sexes) was screened with pooled sera chronic, amicrofilaremic cases of human lymphatic filariasis the Indonesian island Tanjungpinang, where malayi is endemic. Polyclonal antisera raised to purified beta-galactosidase fusion proteins two most highly reactive clones identified a protein Mr 70,000 in all stages examined (microfilariae, L3 and adults) both B. pahangi. Derivation amino acid sequence these...
Resistance of intact mice to infection with the filarial nematode, Brugia malayi is dependent on presence T cells. To investigate role Th2 cells in this protection, a targeted disruption IL-4 gene were infected different developmental stages B. malayi. We examined phenotypic changes immune response and survival each stage these mice. In wild-type mice, adult female worms induce responses, characterized by antigen-specific IgG1 production, elevated IgE, marked secretion splenocytes stimulated...
To evaluate an antigen capture enzyme linked immunosorbent assay (ELISA) which detects a carbohydrate epitope on the excretory-secretory (ES) antigens of Toxocara canis in clinical practice.Serum specimens from healthy adults, patients with acute visceral larva migrans, ocular and inactive toxocariasis, other helminth infections were examined by two site ELISA.Over half (19/28) toxocariasis had positive result contrast to small proportion those disease (1/10) or infection (2/7). False...
The requirement for IL-4 to promote differentiation of naive CD4+ T cells into Th2 effector cell populations was established by classical in vitro studies. More recent vivo data, however, indicate that signaling through the IL-4R is not essential acquisition phenotype. In order reconcile these seemingly contradictory conclusions, we have taken advantage ability excretory/secretory antigens gastrointestinal nematode Nippostrongylus brasiliensis down-regulate Th1 development and drive...