A5006762006- IL-33, ST2, and ILC Pathways
- Parasites and Host Interactions
- Eosinophilic Esophagitis
- Helminth infection and control
- Parasite Biology and Host Interactions
- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- Parasitic Diseases Research and Treatment
- Neonatal Respiratory Health Research
- Food Allergy and Anaphylaxis Research
- Respiratory viral infections research
- Parasitic Infections and Diagnostics
- Pediatric health and respiratory diseases
- RNA regulation and disease
- Renal and related cancers
- Celiac Disease Research and Management
- Vector-Borne Animal Diseases
- Inflammatory Bowel Disease
- Microscopic Colitis
- Extracellular vesicles in disease
- Congenital Diaphragmatic Hernia Studies
- Proteoglycans and glycosaminoglycans research
- Dietetics, Nutrition, and Education
- Blood Coagulation and Thrombosis Mechanisms
- Insect symbiosis and bacterial influences
University of Dundee
2020-2025
Wellcome Trust
2020-2025
University of Edinburgh
2012-2023
University of Regensburg
2023
Centre for Inflammation Research
2014-2020
Queen's Medical Centre
2014-2020
Centre for Immunity, Infection and Evolution
2009-2018
Medical Research Council
2017
The Queen's Medical Research Institute
2016-2017
University of Glasgow
2016
Abstract In mammalian systems RNA can move between cells via vesicles. Here we demonstrate that the gastrointestinal nematode Heligmosomoides polygyrus , which infects mice, secretes vesicles containing microRNAs (miRNAs) and Y RNAs as well a Argonaute protein. These are of intestinal origin enriched for homologues exosome proteins. Administration exosomes to mice suppresses Type 2 innate responses eosinophilia induced by allergen Alternaria. Microarray analysis mouse incubated with in vitro...
Foxp3-expressing regulatory T (T reg) cells have been implicated in parasite-driven inhibition of host immunity during chronic infection. We addressed whether parasites can directly induce reg cells. Foxp3 expression was stimulated naive Foxp3− mice infected with the intestinal helminth Heligmosomoides polygyrus. In vitro, parasite-secreted proteins (termed H. polygyrus excretory-secretory antigen [HES]) induced de novo fluorescence-sorted splenocytes from Foxp3–green fluorescent protein...
Recent studies have demonstrated that many parasites release extracellular vesicles (EVs), yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show secreted by gastrointestinal nematode Heligmosomoides polygyrus are internalized macrophages and modulate activation. EV internalization causes downregulation type 1 2 immune-response-associated molecules (IL-6 TNF, Ym1 RELMα) inhibits expression IL-33 receptor subunit ST2....
Abstract Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the Treg population by secreting products that activate TGF-β signalling, but identity active molecule is unknown. Here we identify an H. mimic ( Hp- TGM) replicates biological and functional properties TGF-β, binding to mammalian receptors inducing human Foxp3 + TGM has no...
Background and Aims The association between hygiene prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study experimental infection with the hookworm Necator americanus was undertaken among a group otherwise healthy people celiac test potential suppress immunopathology induced by gluten. Methods In 21-week, double-blinded, placebo-controlled study, we explored effects N. 20 healthy, helminth-naïve adults well controlled diet. Staged cutaneous...
Helminth parasites such as the nematode Heligmosomoides polygyrus strongly inhibit T helper type 2 (Th2) allergy, well colitis and autoimmunity. Here, we show that soluble excretory/secretory products of H. (HES) potently suppress inflammation induced by allergens from common fungus Alternaria alternata. extract, when administered to mice intranasally with ovalbumin (OVA) protein, induces a rapid (1-48 h) innate response while also priming an OVA-specific Th2 can be evoked 14 days later...
Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in interleukin-33 (IL-33) pathway. Here, we identified H. Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant...
We present immunological data from two clinical trials where the effect of experimental human hookworm (Necator americanus) infection on pathology celiac disease was evaluated. found that basal production Interferon- (IFN-)γ and Interleukin- (IL-)17A duodenal biopsy culture suppressed in hookworm-infected participants compared to uninfected controls. Increased levels CD4+CD25+Foxp3+ cells circulation mucosa are associated with active disease. show this accumulation also occurs during a...
The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and responses hookworm infection in experimentally infected, previously naive individuals from non-endemic areas. collected both peripheral blood duodenal biopsies assess immune response, as well at site adult worm establishment. Our results show that experimental leads a strong Th2 (IL-4, IL-5, IL-9 IL-13) regulatory (IL-10 TGF-β) with some evidence Th1 (IFN-γ IL-2)...
Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about physiological cues activate FALCs pleural cavity and more generally mechanisms controlling activation FALCs. Here we show, using separate models of nematode infection with Litomosoides sigmodontis Altenaria alternata induced acute lung inflammation, inflammation rapidly activates mediastinal pericardial IL-33 produced by FALC...
Heligmosomoides polygyrus (formerly known as Nematospiroides dubius, and also referred to by some H. bakeri) is a gastrointestinal helminth that employs multiple immunomodulatory mechanisms establish chronic infection in mice closely resembles prevalent human infections. has been studied extensively the field of helminth-derived immune regulation found potently suppress experimental models allergy autoimmunity (both with active isolated secreted products). The protocol described this paper...
The kinase FAK coordinates chromatin modifiers and transcription factors to orchestrate evasion of antitumor immune responses.
Rhinovirus-induced neutrophil extracellular traps (NETs) contribute to acute asthma exacerbations; however, the molecular factors that trigger NETosis in this context remain ill-defined. Here, we sought implicate a role for IL-33, an epithelial cell-derived alarmin rapidly released response infection. In mice with chronic experimental (CEA), but not naïve controls, rhinovirus inoculation induced early (1 day post infection; dpi) inflammatory dominated by neutrophils, neutrophil-associated...
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...
Abstract Many helminths, including Brugia malayi, are able to establish long-lived infections in immunocompetent hosts. Growing evidence suggests that the immune system’s failure eliminate parasites is at least partially due effects of regulatory T cells (Tregs). To test whether may directly stimulate host activity, we infected mice with two key stages B. malayi. Both mosquito-borne infective larvae and mature adults i.p. introduced were found preferentially expand proportion CD25+Foxp3+...
ABSTRACT Evidence from human studies and mouse models shows that infection with parasitic helminths has a suppressive effect on the pathogenesis of some inflammatory diseases. Recently, we others have shown effects hookworms reside in their excretory/secretory (ES) products. Here, demonstrate ES products hookworm Ancylostoma caninum (AcES) suppress intestinal pathology model chemically induced colitis. This suppression was associated potent induction type 2 cytokine response characterized by...
Allergic asthma is less prevalent in countries with parasitic helminth infections, and mice infected parasites such as H eligmosomoides polygyrus are protected from allergic airway inflammation. To establish whether suppression of allergy could be mediated by soluble products this helminth, we tested . excretory‐secretory ( HES ) material for its ability to impair When was added sensitising doses ovalbumin, the subsequent response suppressed, ablated cell infiltration, a lower ratio effector...