A5057653322- Parasites and Host Interactions
- Helminth infection and control
- Parasitic Diseases Research and Treatment
- Parasite Biology and Host Interactions
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Parasitic Infections and Diagnostics
- Asthma and respiratory diseases
- Gut microbiota and health
- Mast cells and histamine
- Eosinophilic Esophagitis
- Immune Response and Inflammation
- Helicobacter pylori-related gastroenterology studies
- T-cell and B-cell Immunology
- Inflammatory Bowel Disease
- Dermatology and Skin Diseases
- Parasitic infections in humans and animals
- Gastrointestinal motility and disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Coccidia and coccidiosis research
- Immune responses and vaccinations
- Microscopic Colitis
- Clostridium difficile and Clostridium perfringens research
- Food Allergy and Anaphylaxis Research
- Immune cells in cancer
University of Manchester
2016-2025
Wellcome Centre for Cell-Matrix Research
2013-2025
Manchester Academic Health Science Centre
2017-2022
Centre for Inflammation Research
2019-2022
Centre for Immunity, Infection and Evolution
2021
King Abdulaziz University
2021
University of California, Irvine
2005
Epistem (United Kingdom)
2005
University of Edinburgh
2003
de Duve Institute
2000
Most inbred strains of mouse infected with the intestinal nematode Trichuris muris are resistant to infection expelling parasite before adult worms establish. However, a few susceptible exist that incapable worm expulsion and harbor chronic infections mature worms. Analyses in vitro cytokine production by cells from draining lymph node (mesenteric node) have indicated phenotype is tightly correlated selective expansion helper T (Th) Th1 or Th2 cell subset within mesenteric node, resulting...
The functional integrity of the intestinal epithelial barrier forms a major defense against invading pathogens, including gastrointestinal-dwelling nematodes, which are ubiquitous in their distribution worldwide. Here, we show that an increase rate cell turnover large intestine acts like "epithelial escalator" to expel Trichuris and movement is under immune control by cytokine interleukin-13 chemokine CXCL10. This host protective mechanism pathogens has implications for our wider...
Abstract IL-33 (IL-1F11) binds ST2 (IL-1R4), both of which are associated with optimal CD4+ Th2 polarization. Exogenous drives induction Th2-associated cytokines and pathological changes within the gut mucosa. polarization is also a prerequisite to expulsion intestinal-dwelling nematode Trichuris muris. In this study, we demonstrate that mRNA expressed early during parasite infection susceptible mice can be induced expel by regime exogenous administration. prevents an inappropriate...
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....
De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced cecum mice resistant to Trichuris muris infection. In this study, we investigated role which detected shortly before worm expulsion and associated with production interleukin-13 (IL-13), resistance nematode. Muc5ac-deficient were incapable expelling T. from intestine harbored long-term chronic infections, despite developing strong T(H)2 responses. had elevated levels IL-13 and, surprisingly, an...
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...
A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how contributes intestinal immune homeostasis. Here, we demonstrate that essential for maintenance of balanced CD4(+) T cell responses intestine. Selective deletion cells mice resulted spontaneous inflammation was characterized by aberrant type 2 dietary and microbiota antigens, a loss Foxp3(+) Treg cells. Specific ablation demonstrated directly...
Using a single vector targeting strategy, we have generated mice with combined deficiency of interleukin (IL)-4 and IL-13 to clarify their roles in T helper type 2 (Th2) cell responses. immunological challenges normally characterized by Th2-like response, compared the responses double-deficient those wild-type, IL-4-deficient, IL-13-deficient mice. pulmonary granuloma model, induced Schistosoma mansoni eggs, demonstrate that although eosinophil infiltration, immunoglobulin E, IL-5 production...
We have investigated the influence of mast cells on barrier function intestinal epithelium during nematode infection. Trichinella spiralis infection induces a strong type 2 cytokine-mediated inflammation, resulting in critical mucosal mastocytosis that is known to mediate expulsion parasites from intestine. The host response also characterized by an increase leakiness. show here epithelial permeability markedly elevated infection, with kinetics mirror adaptive immune primary and secondary...
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...
Although T helper 2 (Th2) cytokines are known to be critical in the generation of protective immunity against intestinal helminths mouse models, it is unclear whether they important natural gut helminthiases humans. Therefore, we investigated cytokine production ex vivo whole-blood cultures response Ascaris lumbricoides antigen and mitogen a cross-section community where parasite hyperendemic. The intensity A. infection was significantly reduced after age 11 years. Levels associated with Th2...
Background & AimsHyperplasia of mucin-secreting intestinal goblet cells accompanies a number enteric infections, including infections by nematode parasites. Nevertheless, the precise role mucins in host defense infection is not known. We investigated mucin (Muc2) worm expulsion and immunity model infection.MethodsResistant (BALB/c, C57BL/6), susceptible (AKR), Muc2-deficient mouse strains were infected with nematode, Trichuris muris, expulsion, energy status whipworms, changes mucus/mucins,...
Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine, mainly expressed by epithelial cells, and key to the development of allergic responses. The well-documented involvement TSLP in allergy has led conviction that promotes inflammatory Th2 cell However, we now report interaction with its receptor (TSLPR) no functional impact on protective immune responses after infection 2 helminth pathogens, Heligmosomoides polygyrus Nippostrongylus brasiliensis . Mice deficient...
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...
Infection and systemic inflammation are risk factors for cerebrovascular diseases poststroke infections impair outcome in stroke patients, although the mechanisms of their contribution mostly unknown. No preclinical studies have identified how chronic infection affects ischemic brain damage which key inflammatory mediators involved. We used a well established model gut ( Trichuris muris ) to study contributes injury. show that, mice, that leads Th1-polarized immune response dramatically...