A5076669401- Parasites and Host Interactions
- Helminth infection and control
- IL-33, ST2, and ILC Pathways
- Parasite Biology and Host Interactions
- Immune Cell Function and Interaction
- Eosinophilic Esophagitis
- Parasitic Diseases Research and Treatment
- Mast cells and histamine
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Macrophage Migration Inhibitory Factor
- Immune cells in cancer
- Parasitic Infections and Diagnostics
- Immune Response and Inflammation
- Food Allergy and Anaphylaxis Research
- Allergic Rhinitis and Sensitization
- Cell Adhesion Molecules Research
- Dermatology and Skin Diseases
- Asthma and respiratory diseases
- Gut microbiota and health
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Influenza Virus Research Studies
- Clostridium difficile and Clostridium perfringens research
- Extracellular vesicles in disease
University of Edinburgh
2009-2022
University of Manchester
2019-2022
Manchester Academic Health Science Centre
2021-2022
Institute of Immunology
2014-2021
Victoria University of Wellington
2021
Malaghan Institute of Medical Research
2015-2020
Centre for Inflammation Research
2020
Centre for Immunity, Infection and Evolution
2009-2017
Ashworth College
2014
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...
The intestinal microbiota are pivotal in determining the developmental, metabolic and immunological status of mammalian host. However, tract may also accommodate pathogenic organisms, including helminth parasites which highly prevalent most tropical countries. Both microbes helminths must evade or manipulate host immune system to reside environment, yet whether they influence each other’s persistence remains unknown. We now show that abundance Lactobacillus bacteria correlates positively...
Presentation of peptide:MHCII by RORγ-expressing group 3 innate lymphoid cells (ILC3s), which are enriched within gut tissue, is required for control CD4 T-cell responses to commensal bacteria. It not known whether ILC populations migrate from their mucosal and peripheral sites local draining secondary tissues. Here we demonstrate that ILC3s reside the interfollicular areas lymph nodes, forming a distinct microenvironment observed in nodes. By photoconverting intestinal Kaede mice reveal...
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...
BackgroundEmerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these presently remains ill-defined.MethodsHere, we describe phenotypic functional characteristics of B T cells hospitalized COVID-19 during acute at 3–6 months convalescence.FindingsWe report alterations cell subsets observed were largely recovered convalescent patients. In...
Abstract Numerous population studies and experimental models suggest that helminth infections can ameliorate immuno‐inflammatory disorders such as asthma autoimmunity. Immunosuppressive cell populations associated with include Treg alternatively‐activated macrophages. In previous studies, we showed both CD4 + CD25 Treg, – MLN cells from Heligmosomoides polygyus ‐infected C57BL/6 mice were able to transfer protection against allergic airway inflammation sensitized but uninfected animals. We...
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...
Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. Here we report that lung CD4+ T cells and Group 2 innate lymphoid (ILC2s) work in concert block Nippostrongylus brasiliensis (Nb) development parenchyma within 48 h mice. Immune-damaged larvae have a striking morphological defect is dependent on expansion of IL-13-producing ILC2 cells, activation M2 macrophages. This T-cell requirement can be bypassed by administration IL-2 or...
The nematode Heligmosomoides polygyrus is an excellent model for intestinal helminth parasitism. Infection in mice persists varying lengths of time different inbred strains, with CBA and C57BL/6 being fully susceptible, BALB/c partially so SJL able to expel worms within 2–3 weeks infection. We find that resistance correlates not only the adaptive Th2 response, including IL‐10 but activation innate lymphoid cell macrophage populations. In addition, titer specificity range serum antibody...
Over 25% of the world's population are infected with helminth parasites, majority which colonise gastrointestinal tract. However, no vaccine is yet available for human use, and mechanisms protective immunity remain unclear. In mouse model Heligmosomoides polygyrus infection, vaccination excretory-secretory (HES) antigens from adult parasites elicits sterilising immunity. Notably, three purified HES (VAL-1, -2 -3) sufficient effective vaccination. Protection fully dependent upon specific IgG1...
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...
Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression immune responses to bystander antigens. We show that mice chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in lamina propria mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, partially resistant BALB/c parasite survival positively correlates tTreg numbers....
Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae Heligmosomoides polygyrus, example, encyst in the intestinal submucosa, before emerging as adult worms into duodenal lumen. Adults release immunomodulatory excretory-secretory...
Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present different disease severity. Here, we determined 171 microRNAomes from 58 hospitalized (Cohort 1) of 25 in the same samples. Combining microRNA (miRNA) measurements allowed for discrimination severe cases greater accuracy than using miRNA or alone. Severity group-specific associations between miRNAs COVID-19-associated (e.g., IL6, CCL20) clinical hallmarks...
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...
Abstract Heligmosomoides polygyrus is a widely used gastrointestinal helminth model of long-term chronic infection in mice, which has not been well-characterized at the antigenic level. We now identify major targets murine primary Ab response as subset secreted products H. excretory–secretory (HES) Ag. An immunodominant epitope an O-linked glycan (named A) carried on three highly expressed HES glycoproteins (venom allergen Ancylostoma-secreted protein-like [VAL]-1, -2, and -5), stimulates...
The ability of helminths to manipulate the immune system their hosts ensure own survival is often credited with affecting responses other pathogens. We undertook co-infection experiments in mice determine how infection intestinal helminth Heligmosomoides polygyrus affected parasitological, immunological and physiological outcomes a primary distinct species helminth; lung migratory parasite Nippostrongylus brasiliensis. found that migrating N. brasiliensis larvae were killed lungs H....
Abstract Hookworm infections ( Necator americanus or Ancylostoma duodenale ) represent a major neglected tropical disease, affecting approximately 700 million people worldwide, and can cause severe morbidity due to the need for these worms feed on host blood. N. brasiliensis H. polygrus , both rodent parasites, are two most commonly employed laboratory models of experimental hookworm infection. Both parasites evoke type 2 immune responses, their use has been instrumental in generating...
As part of on-going efforts to control hookworm infection, the "human vaccine initiative" has recognised blood feeding as a feasible therapeutic target for inducing immunity against infection. To this end, molecular approaches have been used identify candidate targets, such Necator americanus (Na) haemoglobinase aspartic protease-1 (APR-1), with immunogenicity profiled in canine and hamster models. We sought accelerate immune analysis these identified targets by developing an appropriate...
Immunity to intestinal helminths is known require both innate and adaptive components of the immune system activated along Type 2 IL-4R/STAT6-dependent pathway. We have found that macrophage migration inhibitory factor (MIF) essential for development effective immunity helminth Heligmosomoides polygyrus, even following vaccination which induces sterile in wild-type mice. A chemical inhibitor MIF, 4-IPP, was similarly compromise anti-parasite immunity. Cellular analyses arm response,...
The C-type lectin superfamily is highly represented in all metazoan phyla so far studied. Many members of this are important innate immune defences against infection, while others serve key developmental and structural roles. Within the superfamily, many proteins contain multiple canonical carbohydrate-recognition domains (CRDs), together with additional non-lectin domains. In report, we have studied two gastrointestinal nematode parasites which widely used experimental rodent systems,...