A5022096253- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Immune Response and Inflammation
- Parasites and Host Interactions
- Immunotherapy and Immune Responses
- Adipokines, Inflammation, and Metabolic Diseases
- T-cell and B-cell Immunology
- Galectins and Cancer Biology
- Cytokine Signaling Pathways and Interactions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Eosinophilic Esophagitis
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Parasite Biology and Host Interactions
- Neonatal Respiratory Health Research
- Immune responses and vaccinations
- SARS-CoV-2 and COVID-19 Research
- Obesity and Health Practices
- Virology and Viral Diseases
- Asthma and respiratory diseases
- Bariatric Surgery and Outcomes
- Omental and Epiploic Conditions
- Reproductive System and Pregnancy
- Fibroblast Growth Factor Research
Lancaster University
2019-2023
University of Edinburgh
2011-2022
Institute of Immunology
2010-2017
Centre for Immunity, Infection and Evolution
2011-2017
British Heart Foundation
2017
Institute of Genetics and Cancer
2017
Edinburgh Cancer Research
2017
Imperial College London
2017
University of Aberdeen
2016
Bristol Royal Hospital for Children
2014-2015
A defining feature of inflammation is the accumulation innate immune cells in tissue that are thought to be recruited from blood. We reveal a distinct process exists which macrophages undergo rapid situ proliferation order increase population density. This inflammatory mechanism occurred during T helper 2 (T(H)2)-related pathologies under control archetypal T(H)2 cytokine interleukin-4 (IL-4) and was fundamental component because exogenous IL-4 sufficient drive through self-renewal. Thus,...
Although dendritic cells (DCs) are adept initiators of CD4+ T cell responses, their fundamental importance in this regard Th2 settings remains to be demonstrated. We have used CD11c–diphtheria toxin (DTx) receptor mice deplete CD11c+ during the priming stage response against parasitic helminth Schistosoma mansoni. DTx treatment significantly depleted DCs from all tissues tested, with 70–80% efficacy. Even incomplete depletion resulted dramatically impaired production cytokines, altering...
Local macrophage clean-up Infection, especially by helminths or bacteria, can cause tissue damage (see the Perspective Bouchery and Harris). Minutti et al. studied mouse models of helminth infection fibrosis. They expressed surfactant protein A (a member complement component C1q family) in lung, which enhanced interleukin-4 (IL-4)-mediated proliferation activation alveolar macrophages. This accelerated clearance reduced lung injury. In peritoneum, boosted for liver repair after bacterial...
Abstract The host defence peptide cathelicidin (LL-37 in humans, mCRAMP mice) is released from neutrophils by de-granulation, NETosis and necrotic death; it has potent anti-pathogen activity as well being a broad immunomodulator. Here we report that powerful Th17 potentiator which enhances aryl hydrocarbon receptor (AHR) RORγt expression, TGF-β1-dependent manner. In the presence of TGF-β1, enhanced SMAD2/3 STAT3 phosphorylation, profoundly suppressed IL-2 T-bet, directing T cells away Th1...
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...
The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides first layer of immunological defense within the abdomen. Here, we investigated mechanisms mediate capture during peritonitis. Single-cell RNA sequencing spatial analysis omental stromal cells revealed surface FALCs were covered by CXCL1+ mesothelial cells, which termed FALC cover cells. Blockade CXCL1 inhibited recruitment aggregation neutrophils at...
Interleukin-4 is a cytokine widely known for its role in CD4 + T cell polarization and ability to alternatively activate macrophage populations. In contrast, the impact of IL-4 on activation function dendritic cells (DCs) poorly understood. We report here that DCs respond both vitro vivo by expression multiple alternative markers with different pattern macrophages. further demonstrate central DC IL-4Rα optimal induction IFNγ responses Th1 Th2 settings, through feedback loop which promotes...
Article17 July 2017Open Access Transparent process Type I interferon is required for T helper (Th) 2 induction by dendritic cells Lauren M Webb orcid.org/0000-0002-1903-7570 Manchester Collaborative Centre Inflammation Research, University of Manchester, UK Search more papers this author Rachel J Lundie Institute Immunology and Infection Immunity, Evolution, Edinburgh, Jessica G Borger Sheila L Brown Lisa Connor Malaghan Medical Wellington, New Zealand Adam NR Cartwright Annette Dougall...
Abstract Dendritic cells (DCs) direct CD4 + T-cell differentiation into diverse helper (Th) subsets that are required for protection against varied infections. However, the mechanisms used by DCs to promote Th2 responses, which important both immunity helminth infection and in allergic disease, currently poorly understood. We demonstrate a key role protein methyl-CpG-binding domain-2 (Mbd2), links DNA methylation repressive chromatin structure, regulating expression of range genes associated...
Global deployment of an effective and safe vaccine is necessary to curtail the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Here, we evaluated a Newcastle virus (NDV)-based vectored-vaccine in mice hamsters for its immunogenicity, safety, protective efficacy against SARS-CoV-2. Intranasal administration recombinant (r)NDV-S expressing spike (S) protein SARS-CoV-2 induced high levels SARS-CoV-2-specific neutralizing immunoglobulin A (IgA)...
Dyslipidemia is a main driver of cardiovascular diseases. The ability macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism key development new treatments. Here, we investigated how adipose tissue regulate post-prandial cholesterol transport. Single-cell RNA sequencing protected bone marrow chimeras demonstrated that ingestion led specific transcriptional activation population resident...
Rapid reprogramming of the macrophage activation phenotype is considered important in defense against consecutive infection with diverse infectious agents. However, setting persistent, chronic functional importance macrophage-intrinsic adaptation to changing environments vs. recruitment new macrophages remains unclear. Here we show that resident peritoneal expanded by nematode Heligmosomoides polygyrus bakeri altered their response Salmonella enterica ser. Typhimurium vitro and vivo. The...
SummarySurvival and genome stability are critical characteristics of healthy cells. DNA palindromes pose a threat to have been shown participate in reaction leading the formation inverted chromosome duplications centered around themselves. There is considerable interest mechanism this rearrangement given its likely contribution instability cancer This study shows that large can be observed Escherichia coli. They formed at site 246 bp interrupted palindrome absence hairpin nuclease SbcCD...
Detrimental effects of maternal smoking on the term placental proteome and steroid-metabolizing activities, hormone levels, were studied by using seven non-smoker smoker placentae. Smoking significantly affected 18% protein spots. The functional networks i) cell morphology, cellular assembly organization, compromise (15 hits) ii) DNA replication, recombination, repair, energy production, nucleic acid metabolism (6 hits). up-regulated such proteins as, SERPINA1, EFHD1 KRT8; down-regulated...
CFB (complement factor B) is elevated in adipose tissue and serum from patients with type 2 diabetes mellitus cardiovascular disease, but the causal relationship to disease pathogenesis unclear. Cfb also of spontaneously hypertensive rat, a well-characterized model metabolic syndrome. To establish role syndrome, we knocked out
Abstract Barth syndrome (BTHS) is an X‐linked disorder characterised by cardiac and skeletal myopathy, growth delay, neutropenia 3‐methylglutaconic aciduria (3‐MGCA). Patients have TAZ gene mutations which affect metabolism of cardiolipin, resulting in low tetralinoleoyl cardiolipin (CL 4 ), increase its precursor, monolysocardiolipin (MLCL), increased MLCL/CL ratio. During development a diagnostic service for BTHS, leukocyte CL was measured 156 controls 34 patients with genetically...
IL‐33 plays an important role in the initiation of type‐2 immune responses, as well enhancement type 2 effector functions. Engagement receptor on macrophages facilitates polarization to alternative activation state by amplifying IL‐4 and IL‐13 signaling IL‐4Rα. also induce macrophage proliferation but involvement this process has not been rigorously evaluated. As expected, vivo delivery induced IL‐4Rα‐dependent serous cavities. proliferate but, unexpectedly, was independent IL‐4Rα signaling....
Dendritic cells (DCs) are the key initiators of T‐helper (Th) 2 immune responses against parasitic helminth Schistosoma mansoni . Although liver is one main sites antigen deposition during infection with this parasite, it not yet clear how distinct DC subtypes in tissue respond to S. antigens vivo , or microenvironment might influence function establishment Th2 response. In study, we show that hepatic subsets undergo activation processes following murine Conventional DCs (cDCs) from...
The response of lymphocytes to phytohaemagglutinin was tested as an index lymphocyte function in patients with acute lymphoblastic leukaemia remission. No significant differences were found the results tests on from treated B.C.G. and those given methotrexate, nor any difference detected between controls.
Gastrointestinal nematode infections cause morbidity and socioeconomic loss in the most deprived communities. The shift context of obesity has led to spatial overlap with endemic gastrointestinal regions resulting emergence a novel comorbidity. Despite this, impact high-fat diet (HFD) on immune-regulated protection against remains largely unknown. We employed murine model infection, Trichuris muris, investigate effect an HFD immune response chronic infection. Surprisingly, diet-induced drove...