A5017258456- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- Immune Response and Inflammation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Salmonella and Campylobacter epidemiology
- Immunodeficiency and Autoimmune Disorders
- SARS-CoV-2 and COVID-19 Research
- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Hematological disorders and diagnostics
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- IL-33, ST2, and ILC Pathways
- Cancer Research and Treatments
- Psoriasis: Treatment and Pathogenesis
- Erythrocyte Function and Pathophysiology
- Bacillus and Francisella bacterial research
- Invertebrate Immune Response Mechanisms
- Cell Image Analysis Techniques
- Telomeres, Telomerase, and Senescence
- Cancer Immunotherapy and Biomarkers
- Antifungal resistance and susceptibility
University of Oxford
2013-2025
King's College London
2022-2025
MRC Weatherall Institute of Molecular Medicine
2013-2025
Blood Cancer UK
2025
MRC Human Immunology Unit
2012-2023
Medical Research Council
2015-2023
King's College Hospital
2023
London Cancer
2023
John Radcliffe Hospital
2019-2020
Institute of Molecular Medicine
2018-2019
The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease 14 disease) 16 unexposed donors, using interferon-γ-based assays peptides spanning SARS-CoV-2 except ORF1. breadth magnitude responses were significantly higher as compared cases. Total spike-specific correlated antibody responses. identified 41...
Following encounter with pathogens, dendritic cells (DC) mature and migrate from peripheral tissues to the T cell areas of secondary lymphoid organs, where they produce regulatory cytokines prime naive lymphocytes. We investigated in two subsets human blood DC expression Toll-like receptors (TLR1 through TLR9) regulation chemokine cytokine production response different maturation stimuli. Myeloid express all TLR except TLR7 TLR9, which are selectively expressed by plasmacytoid DC. respond...
The lethal factor (LF) produced by toxigenic strains of Bacillus anthracis is a Zn(2+)-endopeptidase that cleaves the mitogen-activated protein kinase kinases (MAPKKs) MEK1, MEK2 and MKK3. Using genetic biochemical approaches, we have extended study LF proteolytic specificity to all known MAPKK family members found also MKK4, MKK6 MKK7, but not MEK5. peptide bonds hydrolysed within MAPKKs were identified. Cleavage invariably occurs N-terminal proline-rich region preceding domain, thus...
Abstract The contribution of Th1 and Th17 cells in chronic inflammatory conditions leading to autoimmunity remains highly controversial. In inflamed tissues, production prostaglandins by COX‐2 has been proposed favor responses indirectly increasing IL‐23 blocking IL‐12 release from APC. We report here that prostaglandin E2 (PGE2) can directly modulate cytokine human memory CD4 + T cells. TCR triggering the presence PGE2 increased IL‐17 reduced IFN‐γ freshly isolated or T‐cell clones....
Abstract Mucosal-associated invariant T (MAIT) cells are innate-like that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live Salmonella enterica serovar Paratyphi A, MAIT activated during infection, an effect maintained even after antibiotic treatment. At the peak cell T-cell receptor (TCR)β clonotypes over-represented prior to transiently contract. Select TCRβ expand have stronger TCR-dependent activation than do...
Abstract Mucosal-associated invariant T (MAIT) cells are innate that recognize intermediates of the vitamin B2 biosynthetic pathway presented by monomorphic MR1 molecule. It remains unclear whether, in addition to their cytolytic activity is important antimicrobial defense, MAIT have immune-modulatory functions could enhance dendritic cell (DC) maturation. In this study, we investigated molecular mechanisms dictating interactions between human and DCs demonstrate mature monocyte-derived...
COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding natural immunity to virus, including role SARS-CoV-2-specific T cells. We have conducted a study 42 patients following recovery from COVID-19, 28 mild 14 severe cases, comparing their cell responses those 16 control donors. assessed immune memory using IFNγ based assays with overlapping peptides spanning SARS-CoV-2 apart ORF1. found breadth, magnitude...
The lethal toxin (LeTx) of Bacillus anthracis is the major virulence factor responsible for death infected animals and cytolysis cultured macrophages. Its catalytic component, LF, contains characteristic zinc-binding motif metalloproteases, it binds zinc indirect evidence suggests that this hydrolytic activity essential LeTx cytotoxicity (Limpel et al. 1994; Kochi 1994). To identify substrates we have used yeast two-hybrid system, employing an LF inactive mutant as bait. This approach has...
Significance Peptides are known to be targets of autoreactive T cells that can cause autoimmune diseases. Here we show human recognize self-lipids displayed on the surface by CD1b proteins. A particular lipid is recognized cells, phosphatidylglycerol, present in mammalian mitochondria and bacteria. Therefore, these data define a phospholipid autoantigen released during mitochondrial stress bacterial infection.
Individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease. However, pre-existing immune memory related pathogens cross-reactive against SARS-CoV-2 could influence outcome COVID-19. Here, we investigated potential extent of T cell cross-reactivity severe acute respiratory syndrome 2 (SARS-CoV-2) that can be conferred by other coronaviruses influenza virus, generated an silico map public private CD8+ epitopes between...
Depleting the microenvironment of important nutrients such as arginine is a key strategy for immune evasion by cancer cells. Many tumors overexpress arginase, but it unclear how these cancers, not T cells, tolerate depletion. In this study, we show that tumor cells synthesize from citrulline upregulating argininosuccinate synthetase 1 (ASS1). Under starvation, ASS1 transcription induced ATF4 and CEBPβ binding to an enhancer within ASS1. cannot induce ASS1, despite presence active CEBPβ, gene...
Statins are widely used hypocholesterolemic drugs that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, a rate-limiting enzyme of the mevalonate pathway whose biosynthetic endproduct is cholesterol. As result this activity, statins may perturb composition cell membranes, resulting in lipid raft disruption. Furthermore, by inhibiting protein prenylation, process also dependent on mevalonate, block membrane targeting and activity small GTPases. Antigen uptake, processing presentation...
In this study, we present evidence of differential Th17 responses in human monocyte-derived dendritic cells exposed to the pathogenic Candida albicans or nonpathogenic Saccharomyces cerevisiae. We use different forms microorganisms, cells, hyphae, and spores, as a toolbox dissect role surface mannan fungal immune response. contrast S. cerevisiae yeast cell-induced Th1 response, stimulated with spores C. hyphae induce cellular shifted toward differentiation. The recognition specific...
Lipid transfer proteins, such as molecules of the saposin family, facilitate extraction lipids from biological membranes for their loading onto CD1d molecules. Although it has been shown that prosaposin-deficient mice fail to positively select invariant natural killer T (iNKT) cells, remains unclear whether saposins can endogenous iNKT cell agonists in periphery during inflammatory responses. In addition, is saposins, addition loading, also promote dissociation bound To address these...
Enteric fever is a systemic infection caused by Salmonella Typhi or Paratyphi A. In many endemic areas, these serovars co-circulate and can cause multiple infection-episodes in childhood. Prior exposure thought to confer partial, but incomplete, protection against subsequent attacks of enteric fever. Empirical data support this hypothesis are limited, there few studies describing the occurrence heterologous-protection between closely related serovars. We performed challenge-re-challenge...
Abstract The role of src‐family tyrosine kinases in LPS‐induced DC maturation has not been fully addressed. We show that LPS induces activation c‐Src and Lyn human DC. Inhibition these kinasesby PP1 uncoupled cytokine production from the up‐regulation costimulatory molecules, resulting still capable stimulating T cell proliferation but much less efficient inducing Th1 differentiation. This is first example a pharmacological inhibitor able to modulate capacity induce particular type immune...