A5058808427- Parasites and Host Interactions
- Helminth infection and control
- Parasite Biology and Host Interactions
- Parasitic Infections and Diagnostics
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Autoimmune Neurological Disorders and Treatments
- Pneumocystis jirovecii pneumonia detection and treatment
- Gut microbiota and health
- Immune cells in cancer
- Antimicrobial Peptides and Activities
- vaccines and immunoinformatics approaches
- Eosinophilic Esophagitis
- Parasitic Diseases Research and Treatment
- Cardiovascular Disease and Adiposity
- Reproductive System and Pregnancy
- Eosinophilic Disorders and Syndromes
- RNA regulation and disease
- Gastrointestinal motility and disorders
- Child Nutrition and Water Access
- Chemokine receptors and signaling
University of Manchester
2015-2024
Manchester Academic Health Science Centre
2018-2021
Institute of Immunology
2020
Abstract Obesity impairs the relaxant capacity of adipose tissue surrounding vasculature (PVAT) and has been implicated in resultant obesity-related hypertension impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated role eosinophils mediating normal PVAT function. Healthy elicits an anti-contractile effect, which was lost mice deficient eosinophils, mimicking obese phenotype, restored upon eosinophil reconstitution. Ex vivo studies...
Parasitic nematodes infect hundreds of millions people and farmed livestock. Further, plant parasitic result in major crop damage. The pipeline therapeutic compounds is limited parasite resistance to the existing anthelmintic a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, algorithm (Paragon) which allows screening that effect on motility development worms. validated its utility by determining...
Neurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators structural consequences CD8(+) T lymphocyte (CTL) attack on neurons in vivo. In a viral encephalitis model mice, disease depended CTL-derived interferon-γ (IFN-γ) IFN-γ signaling. Downstream STAT1 phosphorylation nuclear translocation were associated dendrite synapse loss...
Resistance to the intestinal parasitic helminth Trichuris muris requires T-helper 2 (TH2) cellular and associated IgG1 responses, with expulsion typically taking up 4 weeks in mice. Here, we show that time-of-day of initial infection affects efficiency worm expulsion, strong TH2 bias early morning-infected Conversely, mice infected at start night delayed resistance infection, this is feeding-driven metabolic cues, such feeding restriction day-time normally nocturnal-feeding disrupts...
Background Mouse angiogenin 4 (Ang4) has previously been described as a Paneth cell–derived antimicrobial peptide important in epithelial host defence the small intestine. However, source for Ang4 large intestine, which is devoid of cells, not defined. Methodology/Principal Findings Analysis was performed on expression colonic tissue by qPCR and immunohistochemistry following infection with intestine dwelling helminth parasite Trichuris muris. This demonstrated an increase resistant BALB/c...
Infection is a recognised risk factor for Alzheimer's disease (AD) and can worsen symptoms in established disease. AD patients have higher rates of infection are more likely to require hospital admissions due infections than individuals without dementia. Infections also been found increase the those over 84 years age being diagnosed with However, few studies investigated immune responses AD.
Trichuris trichiura is a human parasitic whipworm infecting around 500 million people globally, damaging the physical growth and educational performance of those infected. Current drug treatment options are limited lack efficacy against worm, preventing an eradication programme. It therefore important to develop new treatments for trichuriasis. Using muris, established model T. trichiura, we screened library 480 novel drug-like small molecules compounds causing paralysis ex vivo adult...
The human whipworm Trichuris trichiura is a parasite that infects around 500 million people globally, with consequences including damage to physical growth and educational performance. Current drugs such as mebendazole have notable lack of efficacy against whipworm, compared other soil-transmitted helminths. Mass drug administration programs are therefore unlikely achieve eradication new treatments for trichuriasis desperately needed. All current control strategies focus on post-infection...
IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by is equally crucial for the differentiation a population T-bet+ regulatory (Treg) specialized inhibit Th1 immune responses. Conditional deletion receptor in but not Treg resulted severe defect this specific subset, leading exacerbated pathology during parasitic infections. Mechanistically, IFNγ-unresponsive failed produce sufficient amount IL-27, cytokine required...
ABSTRACT Experimental cerebral malaria (ECM) is a gamma interferon (IFN-γ)-dependent syndrome. However, whether IFN-γ promotes ECM through direct and synergistic targeting of multiple cell populations or by acting primarily on specific responsive type currently unknown. Here, using panel cell- compartment-specific receptor 2 (IFN-γR2)-deficient mice, we show that causes signaling within both the hematopoietic nonhematopoietic compartments. Mechanistically, IFN-γR exerts additive effects in...
Eosinophils are innate immune cells present in the intestine during steady state conditions. An intestinal eosinophilia is a hallmark of many infections and an accumulation eosinophils also observed inflammatory disorders. Classically function has been associated with tissue destruction, due to release cytotoxic granule contents. However, recent evidence demonstrated that eosinophil plays more diverse role system than previously acknowledged, including shaping adaptive responses providing...
Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of benzimidazole drugs, mainstay preventative chemotherapy for whipworm, together parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We seeking develop new anthelmintic drugs specifically activity against whipworm as a priority previously...
The intestinal nematode parasite Trichuris muris dwells in the caecum and proximal colon driving an acute resolving inflammation dominated by presence of macrophages. Notably, these macrophages are characterised their expression RELMα during resolution phase infection. RELMα+ macrophage phenotype associates with alternatively activated work other model systems has demonstrated that balance classically is critically important enabling inflammation. Moreover, context type 2 immunity,...
Trichuris spp. (whipworms) are intestinal nematode parasites which cause chronic infections associated with significant morbidities. muris in a mouse is the most well studied of whipworms and research on this species has been approached from number different disciplines. Research T. laboratory provided vital insights into host–parasite interaction through analyses immune responses to infection, identifying factors underpinning host susceptibility resistance. Laboratory studies have also...
Trichuris muris , is the murine parasite and widely deployed model for human whipworm trichiura a that infects around 500 million people globally. Trichuriasis classical disease of poverty with cycle re-infection due to continual exposure humans, particularly children, infective eggs, which contaminate soil in endemic areas. Indeed, modelling studies trichuriasis have demonstrated low efficacy rate current anthelmintics combined high possibility from reservoir eggs within environment, mean...
Abstract The IgMi mouse has normal B cell development; its cells express an IgM receptor but cannot class switch or secrete antibody. Thus, the offers a model system by which to dissect out antibody-dependent and antibody-independent function. Here, we provide first detailed characterisation of post- Trichuris muris ( T. ) infection, describing expulsion phenotype, cytokine production, gut pathology changes in T regulatory cells, follicular helper germinal centre addition RNA sequencing (RNA...
Trichuris muris is a natural mouse helminth pathogen which establishes infection specifically in the caecum and proximal colon. The rapid expulsion of T. resistant strains associated with induction protective T helper cell type 2 (Th2)-polarized immune response. Susceptible strains, contrast, mount an inappropriate Th1 response to infection. Expression chemokine CXCL13 by stromal follicular dendritic cells attracts CXCR5-expressing towards B-cell follicles. Previous studies using complex...
Abstract The human whipworm Trichuris trichiura is a parasite that infects around 500 million people globally, with consequences including damage to physical growth and educational performance. Current drugs such as mebendazole have notable lack of efficacy against whipworm, compared other soil-transmitted helminths. Mass drug administration programs are therefore unlikely achieve eradication new treatments for trichuriasis desperately needed. All current control strategies focus on...
Intestinal epithelial homeostasis is maintained by intrinsic and extrinsic signals. The signals include those provided mesenchymal cell populations that surround intestinal crypts further facilitated the extracellular matrix (ECM), which modulated proteases such as metalloproteinases (MMPs). Extrinsic ensure an appropriate balance between proliferation differentiation. This study explores role of MMP17, preferentially expressed smooth muscle cells in intestine, during immunity to infection....