A5059026603- Parasites and Host Interactions
- Parasite Biology and Host Interactions
- Helminth infection and control
- Gut microbiota and health
- IL-33, ST2, and ILC Pathways
- Parasitic Infections and Diagnostics
- Asthma and respiratory diseases
- Insect Utilization and Effects
- Immune Cell Function and Interaction
- Eosinophilic Esophagitis
- Parasitic Diseases Research and Treatment
- Parasitic infections in humans and animals
- Amoebic Infections and Treatments
- RNA modifications and cancer
- Insects and Parasite Interactions
- Clostridium difficile and Clostridium perfringens research
- Gastrointestinal motility and disorders
- Insect symbiosis and bacterial influences
- Epigenetics and DNA Methylation
- Viral gastroenteritis research and epidemiology
- Immune cells in cancer
- Diverse Scientific Research Studies
- Vector-borne infectious diseases
- Insect behavior and control techniques
- Vitamin D Research Studies
University of Manchester
2012-2025
Wellcome Centre for Cell-Matrix Research
2018-2022
Manchester Academic Health Science Centre
2018-2022
Centre for Inflammation Research
2019-2021
Centre for Immunity, Infection and Evolution
2021
University of Cambridge
1995
Liverpool School of Tropical Medicine
1993-1994
Ninewells Hospital
1992
The inhabitants of the mammalian gut are not always relatively benign commensal bacteria but may also include larger and more parasitic organisms, such as worms protozoa. At some level, all these organisms capable interacting with each other. We found that successful establishment chronically infecting nematode Trichuris muris in large intestine mice is dependent on microflora coincident modulation host immune response. By reducing number animal, we significantly reduced hatched T. eggs....
Macrophages in the healthy intestine are highly specialized and usually respond to gut microbiota without provoking an inflammatory response. A breakdown this tolerance leads bowel disease (IBD), but mechanisms by which intestinal macrophages normally become conditioned promote microbial unclear. Strong epidemiological evidence linking disruption of antibiotic use early life IBD indicates important role for modulating immunity. Here, we show that causes hyperresponsive bacterial stimulation,...
Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled comprehensive investigation into effects T. infection on faecal microbiota mice following successful clearance infection. Communities were profiled using DGGE, 454 pyrosequencing, metabolomics. Changes microbial composition occurred between 14 28 days post infection, resulting...
Abstract Mice in which either the IL-4 or IL-13 gene has been disrupted (IL-4 KO and KO) were susceptible to infection with intestinal nematode Trichuris muris, whereas their wild-type littermates highly resistant expelled parasite. mice showed diminished Th2-type responses T. muris also failed produce parasite-specific IgG1 Abs. Although made reduced early infection, they capable of generating strong at later time points unable regulate magnitude Ab isotype response. These results confirm...
Intestinal parasite selects for its own intestinal microbiota from the host and modifies host’s microbiota.
Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes only distantly related to Caenorhabditis elegans and have evolved occupy an unusual niche, tunneling through epithelial cells of the large intestine. We report here whole-genome sequences human-infective Trichuris trichiura mouse laboratory model muris. On basis whole-transcriptome analyses, we identify many genes expressed a sex- or life stage-specific manner characterize...
Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark eukaryotes. Once introduced, 5meC can be maintained through replication by activity ‘maintenance’ methyltransferases (DNMTs). Despite their ancient origin, methylation pathways differ widely across animals, such that either confined to transcribed genes or lost altogether several lineages. We used comparative epigenomics investigate evolution methylation. Although model nematode Caenorhabditis elegans lacks...
Parasitic helminths such as the Trichuris whipworms contribute to significant disease and morbidity in humans other animals. They cause prolonged infections despite intact immune systems of their hosts, persistence is increasingly attributed immunomodulatory activities secreted products. We examined p43 (Tm-DLP-1) protein muris that comprises about 95% by adult parasite, known bind matrix proteoglycans, have IL-13-neutralising activity. show here worm-derived purified from secretions binds...
In vivo manipulation of cytokine and/or receptor expression has previously shown that resistance to infection with the caecum-dwelling helminth Trichuris muris is dependent on interleukin (IL)-4 and IL-13 while susceptibility associated a T helper cell type 1 (Th1) response. Using gene-targeted mice deficient in tumor necrosis factor (TNF) signaling anti–TNF-α monoclonal antibody treatment, we have extended these studies reveal critical role for TNF-α regulation Th2 cytokine–mediated host...
Abstract Resistance and susceptibility to the intestinal nematode Trichuris muris has been shown be dependent upon induction of T helper type 2 (T h 2) or 1 cells, respectively. This study demonstrates that in a normally resistant strain mouse, i.e. BALB/K which mounts dominant response, sub‐threshold levels infection (< 40 eggs) can survive become sexually mature adult worms (10–20 adults). The immunological basis this phenomenon was found dramatically altered polarization CD4 response....
In murine models of Schistosoma mansoni infection, egg production is associated with a switch from T helper cell (Th)1- to Th2-type responses both schistosome-specific and unrelated antigens. Polyparasitism common in human populations within S. endemic areas. We have, therefore, examined whether coinfection could affect the outcome second parasitic through Th2 cytokine-dependent modifications host immune response. find that when mice susceptible infection gut nematode Trichuris muris are...
Abstract Gastrointestinal nematodes, such as Trichuris trichiura (human whipworm), are a major source of morbidity in humans and their livestock. There is paucity commercially available vaccines against these parasites, vaccine development for T. has been impeded by lack known host protective antigens. Experimental vaccinations with muris (murine whipworm) soluble Excretory/Secretory (ES) material have demonstrated that it possible to induce immunity mice; however, the potential...
Host immunity to parasitic nematodes requires the generation of a robust type 2 cytokine response, characterized by production interleukin 13 (IL-13), which drives expulsion. Here, we show that infection with helminths in intestine also induces an ILC2-driven, IL-13–dependent goblet cell hyperplasia and increased mucins (Muc5b Muc5ac) at distal sites, including lungs other mucosal barrier sites. Critically, priming lung tissue through mucin inhibits progression subsequent migratory helminth...
Infection by soil transmitted parasitic helminths, such as Trichuris spp, are ubiquitous in humans and animals but the mechanisms determining persistence of chronic infections poorly understood. Here we show that p43, single most abundant protein T. muris excretions/secretions, is non-immunogenic during infection has an unusual sequence structure containing subdomain homology to thrombospondin type 1 interleukin (IL)-13 receptor (R) α2. Binding p43 IL-13, key effector cytokine responsible...
Female IL-4 knockout (KO) mice on a C57BL/6 background (F4KOC57) are susceptible to infection with the cecal-dwelling nematode Trichuris muris whereas wild-type resistant and expel parasite. In this study we show that in sharp contrast, female KO BALB/c (F4KOB/c) as mice. Although F4KOC57 make negligible levels of all type 2 cytokines, F4KOB/c were capable producing significant antigen-specific IL-13 (a cytokine shown be critical resistance T. muris). To examine if was functional importance,...
Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the intestine of their hosts, causing chronic disease humans and other mammals. How first-stage larvae invade host epithelia establish infection remains unclear. Here we investigate early events using both Trichuris muris infections mice murine caecaloids, first in-vitro system for whipworm organoid model live helminths. We show degrade mucus layers to access cells. In syncytial tunnels, completely...
Abstract Resistance and susceptibility to the intestinal parasite Trichuris muris has been shown be due a dominant T helper 2 (Th2) Th1 response, respectively. The factors determining initial polarization of immune response remain largely unresolved, although cytokine environment at time antigen presentation clearly plays an essential role. Interleukin (IL)‐12, produced mainly by macrophages, dendritic cells, other monocytes important in driving strong stimulating production interferon...
Abstract Chronic infection by the gastrointestinal nematode Trichuris muris in susceptible AKR mice, which mount a Th1 response, is associated with IL-27p28 expression cecum. In contrast to wild-type mice that lack WSX-1/IL-27R gene fail harbor chronic infection, having significantly lower responses. The level of Ag-specific IFN-γ-positive cells WSX-1 knockout (KO) was found be CD4+ T cell specific, and KO also had increased levels IL-4-positive cells. Polyclonal activation mesenteric lymph...
BALB/c mice immunized with radiation attenuated third stage larvae of the filarial nematode Brugia pahangi are strongly immune to challenge infection. Investigation profile cytokines secreted by spleen cells from stimulated in vitro either parasite Ag or Con A revealed high levels IL-5 and IL-9 moderate IL-4. In contrast, secretion IFN-gamma animals was negligible. Spleen control low all assayed. Levels parasite-specific IgE were significantly elevated a peripheral blood eosinophilia...