A5082043968- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Infectious Diseases and Tuberculosis
- Pneumocystis jirovecii pneumonia detection and treatment
- Peptidase Inhibition and Analysis
- Diagnosis and treatment of tuberculosis
- Immune Cell Function and Interaction
- Protease and Inhibitor Mechanisms
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Pneumonia and Respiratory Infections
- 3D Printing in Biomedical Research
- Immune cells in cancer
- Chronic Obstructive Pulmonary Disease (COPD) Research
- COVID-19 and Mental Health
- Innovative Microfluidic and Catalytic Techniques Innovation
- Sarcoidosis and Beryllium Toxicity Research
- Infection Control and Ventilation
- Cell Image Analysis Techniques
- T-cell and B-cell Immunology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- SARS-CoV-2 and COVID-19 Research
- Asthma and respiratory diseases
- Bacterial Infections and Vaccines
- Microfluidic and Bio-sensing Technologies
NIHR Southampton Biomedical Research Centre
2017-2024
University of Southampton
2015-2024
National Institute for Health Research
2014-2024
University Hospital Southampton NHS Foundation Trust
2013-2022
NIHR Southampton Respiratory Biomedical Research Unit
2013-2022
NIHR Imperial Biomedical Research Centre
2018-2021
Southampton City Council
2021
Imperial College London
2010-2019
Wellcome Trust
2011-2019
Hammersmith Hospital
2005-2018
Background Mycobacterium tuberculosis, the causative agent of still represents a major public health threat in many countries. Bioluminescence, production light by luciferase-catalyzed reactions, is versatile reporter technology with multiple applications both vitro and vivo. In vivo bioluminescence imaging (BLI) one its most outstanding uses allowing non-invasive localization luciferase-expressing cells within live animal. Despite extensive use luminescent reporters mycobacteria, resultant...
Calcidiol, the major circulating metabolite of vitamin D, supports induction pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates calcidiol concentrations, and thus has a potential role prevention treatment infection. The immunomodulatory effects administering to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted detailed longitudinal study antigen-stimulated immune ninety-five patients receiving...
Tuberculosis (TB), a chronic infectious disease of global importance, is facing the emergence drug-resistant strains with few new drugs to treat infection. Pulmonary cavitation, hallmark established disease, associated very high bacillary burden. Cavitation may lead delayed sputum culture conversion, drug resistance, and transmission The host immunological reaction Mycobacterium tuberculosis implicated in driving development TB cavities. characterized by matrix-degrading phenotype which...
Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate spread M. tuberculosis. The mechanism matrix destruction resulting in cavitation is not well defined. Neutrophils emerging as key mediators TB immunopathology their influx associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved TB-associated using a cellular model, cohort 108 patients, separate patient lung biopsies. Neutrophil-derived...
Mycobacterium tuberculosis can cause lung tissue damage to spread, but the mechanisms driving this immunopathology are poorly understood. The breakdown of matrix involves MMPs, which have a unique ability degrade fibrillar collagens at neutral pH. To determine whether MMPs play role in (TB), we profiled and their inhibitors, inhibitor metalloproteinases (TIMPs), sputum bronchoalveolar lavage fluid from patients with TB symptomatic controls. MMP-1 concentrations were significantly increased...
<h3>Background</h3> It is unknown whether lesions in human TB are hypoxic or this influences disease pathology. Human characterised by extensive lung destruction driven host matrix metalloproteinases (MMPs), particularly collagenases such as metalloproteinase-1 (MMP-1). <h3>Methods</h3> We investigated tissue hypoxia five patients with PET imaging using the tracer [<sup>18</sup>F]-fluoromisonidazole ([<sup>18</sup>F]FMISO) and immunohistochemistry. studied regulation of MMP secretion primary...
Rationale: Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for 30 years. (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined no current antituberculous therapy reduces host damage.Objectives: To investigate MMP in patients with TB without coinfection determine the potential of doxycycline inhibit MMPs decrease...
Compounds that inhibit matrix metalloproteinases should be tested for their ability to limit tuberculosis morbidity and mortality.
A growing body of evidence suggests that studying cell biology in classical two‐dimensional formats, such as culture plasticware, results misleading, non‐physiological findings. This paper describes the optimization a microsphere‐based system permitting 3D incorporating physiological extracellular matrix components. Bio‐electrospraying, most advanced method currently available, is used to produce microspheres containing THP‐1 cells model line. The bio‐electrospraying parameters nozzle size,...
Previously, we developed a 3-dimensional cell culture model of human tuberculosis (TB) and demonstrated its potential to interrogate the host-pathogen interaction (Tezera et al., 2017a). Here, use investigate mechanisms whereby immune checkpoint therapy for cancer paradoxically activates TB infection. In patients, PD-1 is expressed in Mycobacterium (Mtb)-infected lung tissue but absent areas immunopathology. microsphere model, ligands are up-regulated by infection, PD-1/PD-L1 axis further...
A central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism pathology demonstrate collagen may be a critical initial event, causing as opposed resulting from it. In human granulomas, regions map areas necrosis. mice, transgenic expression metalloproteinase 1 causes necrosis, pathological hallmark tuberculosis. Collagen principal difference between humanised mice wild-type...
Abstract Active tuberculosis ( TB ) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity mortality. Matrix metalloproteinases MMPs ), in particular MMP ‐1, are implicated pathogenesis. We explored the mechanisms relating / TIMP imbalance cavity formation a modified rabbit model of cavitary . Our resulted consistent progression consolidation human‐like cavities (100% by...
<h3>Background</h3> Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and drive tissue remodelling, key processes in pathogenesis of COPD. The development small airway disease has been identified as a critical mechanism early airflow obstruction but contribution MMPs human is poorly characterised. <h3>Objectives</h3> We investigated role inflammatory cytokines lung by quantifying levels determining relationships with pathological components...
T cell immunity is essential for the control of tuberculosis (TB), an important disease lung, and generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory cells (Trms) are superior at controlling many pathogens, including Mycobacterium (M. tuberculosis), can be quite different from those circulation. Using freshly resected lung tissue, individuals with active or previous TB, we identified distinct CD4+ CD8+ Trm-like clusters...
Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease in patients particular genetic ancestry, and elicit different patterns cytokine chemokine secretion when cultured with human macrophages vitro. Circulating antigen-stimulated concentrations these inflammatory mediators might therefore be expected to vary significantly between ethnic origin. Studies characterise such variation, determine whether it relates host or bacillary factors, have not been conducted. We...
Introduction Tuberculosis (TB) destroys lung tissues and this immunopathology is mediated in part by Matrix Metalloproteinases (MMPs). There are no data on the relationship between local tissue MMPs concentrations, anti-tuberculosis therapy sputum conversion. Materials Methods Induced was collected from 68 TB patients 69 controls a cross-sectional study. concentrations were measured Luminex array, TIMP ELISA correlated with disease severity score (TBscore). 46 then studied longitudinally at...
Cell biology differs between traditional cell culture and 3-dimensional (3-D) systems, is modulated by the extracellular matrix. Experimentation in 3-D presents challenges, especially with virulent pathogens. Mycobacterium tuberculosis (Mtb) kills more humans than any other infection characterised a spatially organised immune response matrix remodelling. We developed system incorporating mycobacteria, primary human blood mononuclear cells collagen-alginate to dissect host-pathogen...