A5001501626- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
- IL-33, ST2, and ILC Pathways
- Phagocytosis and Immune Regulation
- Influenza Virus Research Studies
- Clinical Nutrition and Gastroenterology
- Liver Diseases and Immunity
- Diabetes and associated disorders
- Liver Disease Diagnosis and Treatment
- Microbial infections and disease research
- Infant Nutrition and Health
- Hepatitis Viruses Studies and Epidemiology
- Biosensors and Analytical Detection
- Animal health and immunology
- Systemic Lupus Erythematosus Research
- Escherichia coli research studies
- Galectins and Cancer Biology
- Entrepreneurship Studies and Influences
- Pediatric Hepatobiliary Diseases and Treatments
- Viral-associated cancers and disorders
- Amoebic Infections and Treatments
- Immune responses and vaccinations
University of Oxford
2011-2020
Medawar Building for Pathogen Research
2015-2020
Peter Doherty Institute
2018-2020
The University of Melbourne
2018-2020
Inserm
2014
Université Claude Bernard Lyon 1
2014
Centre National de la Recherche Scientifique
2014
Centre de Recherche en Cancérologie de Lyon
2014
Leiden University Medical Center
2011
Abstract Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT also activated during human viral infections vivo . activation was observed infection with dengue virus, hepatitis C virus influenza virus. This activation—driving cytokine release Granzyme B upregulation—is TCR-independent but dependent on IL-18 synergy IL-12, IL-15 and/or interferon-α/β. levels cell correlate disease severity acute infection....
Human macrophages are specialised hosts for HIV-1, dengue virus, Leishmania and Mycobacterium tuberculosis. Yet macrophage research is hampered by lack of appropriate cell models modelling infection these human pathogens, because available myeloid lines are, definition, not terminally differentiated like tissue macrophages. We describe here a method deriving monocytes from Pluripotent Stem Cells which improves on previously published protocols in that it uses entirely defined, feeder-...
Background & AimsMucosal-Associated Invariant T (MAIT) cells are innate-like characterised by the invariant TCR-chain, Vα7.2-Jα33, and restricted MR1, which presents bacterial vitamin B metabolites. They important for antibacterial immunity at mucosal sites; however, detailed characteristics of liver-infiltrating MAIT (LI-MAIT) their role in biliary immune surveillance remain unexplored.MethodsThe phenotype intrahepatic localisation human LI-MAIT was examined diseased normal livers. cell...
Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which abundant in human lungs and can contribute to protection against pulmonary bacterial infection. MAIT also activated during viral infections, yet it remains unknown whether play a significant protective or even detrimental role infections vivo. Using murine experimental challenge with two strains of influenza A virus, we show that accumulate early infection, upregulation CD25, CD69 Granzyme...
Mucosal‐associated invariant T (MAIT) cells are an abundant innate‐like lymphocyte population that enriched in liver and mucosal tissues. They restricted by MR1, which presents antigens derived from a metabolic precursor of riboflavin synthesis, pathway present many microbial species, including commensals. Therefore, MR1‐mediated MAIT cell activation must be tightly regulated to prevent inappropriate immunopathology. Using vitro model primary human cells, we investigated the mechanisms it is...
CD161 is a C-type lectin like receptor expressed on the majority of Natural Killer (NK) cells; however, significance expression NK cells has not been comprehensively investigated. Recently we found that identifies transcriptional and innate functional phenotype shared across various T cell populations. Using mass cytometry microarray experiments, demonstrate this extends to cells. marks have retained ability respond cytokines during their differentiation, lost upon cytomegalovirus...
Mucosal-associated invariant T (MAIT) cells are innate-like abundant in humans that can be activated a TCR-independent manner by inflammatory and antiviral cytokines. In humans, the capacity for activation is functionally linked to transcriptional program identified expression of C-type lectin receptor, CD161. addition MAIT cells, it has been demonstrated subset γδT expresses CD161 cytokine stimulation. this study, we sought clarify nature cytokine-responsive human cells. We could link on...
Mucosal-associated invariant T (MAIT) cells represent an innate T-cell population that can recognize ligands generated by the microbial riboflavin synthesis pathway, presented via major histocompatibility complex class I–related molecule (MR1). Streptococcus pneumoniae is a human pathogen also associated with commensal carriage; thus, host control at mucosal interface critical. The recognition of pneumococci MAIT has not been defined nor have genomics and transcriptomics operon. We observed...
Macrophages constitute an important reservoir of HIV-1 infection, yet entry into these cells is poorly understood due to the difficulty in genetically manipulating primary macrophages. We developed effective genetic approach manipulate sub-cellular distribution CD4 macrophages, and investigated how this affects pathway. Pluripotent Stem Cells (PSC) were transduced with lentiviral vectors designed location then differentiated modified infection was assessed by performing assays that measure...
Both HIV and HCV infections feature increased microbial translocation (MT) gut dysbiosis that affect immune homeostasis disease outcome. Given their commitment to antimicrobial mucosal immunity, we investigated mucosal-associated invariant T (MAIT) cells Vα7.2+CD161- T-cell frequency/function possible associations with MT dysbiosis, in chronic and/or infections. We enrolled 56 virally-infected (VI) patients (pts): 13 HIV+ on suppressive cART (HIV-RNA<40cp/ml), HCV+ naive DAA (direct-acting...
Human cytomegalovirus (HCMV) has a double-stranded DNA genome of approximately 235 Kbp that is structurally complex including extended GC-rich repeated regions. Genomic recombination events are frequent in HCMV cultures but have also been observed vivo. Thus, the assembly whole genomes from technologies producing shorter than 500 bp sequences technically challenging. Here we improved reconstruction full by means hybrid, de novo genome-assembly bioinformatics pipeline upon data generated...
The Epstein-Barr virus (EBV)-encoded immune evasion protein BNLF2a inhibits the transporter associated with antigen processing (TAP), thereby downregulating HLA class I expression at cell surface. As a consequence, recognition of EBV-infected cells by cytotoxic T is impaired. Here, we show that sequence polymorphism observed natural EBV isolates, evidence for positive selection. Despite these mutations, variants efficiently reduce surface levels. This conservation function during evolution...
Abstract Upon activation, CD4+ T cells release cytokines, chemokines, and other soluble factors that influence the kinetics of HIV-1 replication in macrophages (Mϕ). In this article, we show activation human primary suppresses early stages Mϕ by downregulating main cellular receptor for virus CD4. The secreted responsible effect have a molecular mass greater than conventional are independent Th1 or Th2 polarization, not IFN-γ, IL-16, RANTES, macrophage inhibitory factor, as revealed cytokine...
CCR5 (CD195) is a receptor for the chemokines RANTES, MIP-1α, and MIP-1β used by HIV-1 as co-receptor entry into macrophages CD4+ T cells. exists in multiple conformations membrane present at low levels on human macrophages, making it difficult to detect. Nine commercially available anti-CCR5 monoclonal antibodies were evaluated their specificity recognition of expressed macrophages. Unexpectedly, we found that three nine clones tested displayed substantial background binding negative cells,...
Abstract Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which abundant in human lungs and can contribute to protection against pulmonary bacterial infection. MAIT also activated during viral infections, yet it remains unknown whether play a significant protective or even detrimental role infections vivo . Using murine experimental challenge with two strains of influenza A virus, we show that accumulated were early infection, upregulation...
MAIT cells are abundant, highly evolutionarily conserved innate-like lymphocytes expressing a semi-invariant T cell receptor (TCR), which recognizes microbially derived small intermediate molecules from the riboflavin biosynthetic pathway. However, in addition to their TCR-mediated functions they can also be activated TCR-independent manner via cytokines including IL-12, -15, -18, and type I interferon. Emerging data suggest that expanded by range of viral infections, significantly...
<b>Background:</b> Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which abundant in human lungs and can contribute to protection against pulmonary bacterial infection. However, whilst they also activated during viral infections, it is unknown whether MAIT play a significant protective or even detrimental role infections vivo. <b>Aims objectives:</b> To determine – either influenza A infection <b>Methods:</b> We used major histocompatibility...
Abstract Mucosal Associated Invariant T (MAIT) cells represent an innate cell population of emerging significance. These abundant can recognize ligands generated by microbes utilizing the riboflavin synthesis pathway, presented via major histocompatibility complex (MHC) class I-related molecule MR1 and binding specific receptors (TCR). They also possess functional programme allowing microbial sensing in a cytokine-dependent, TCR-independent manner. Streptococcus pneumoniae is human pathogen...
MAIT cells are abundant, highly evolutionarily conserved innate-like lymphocytes expressing a semi-invariant T cell receptor (TCR), which recognizes microbially derived small intermediate molecules from the riboflavin biosynthetic pathway. However, in addition to their TCR-mediated functions they can also be activated TCR-independent manner via cytokines including IL-12, -15, -18, and type I interferon. Emerging data suggest that expanded by range of viral infections, significantly...