A5031591427- Respiratory viral infections research
- Immune Cell Function and Interaction
- Neonatal Respiratory Health Research
- IL-33, ST2, and ILC Pathways
- Asthma and respiratory diseases
- Pneumonia and Respiratory Infections
- Nursing Roles and Practices
- Biomedical Ethics and Regulation
- Congenital Diaphragmatic Hernia Studies
- Research on Leishmaniasis Studies
- T-cell and B-cell Immunology
- Parasites and Host Interactions
- Pancreatitis Pathology and Treatment
- Trypanosoma species research and implications
- Ethics in medical practice
- Immune cells in cancer
- Diagnosis and Treatment of Venous Diseases
- Nursing Diagnosis and Documentation
- Palliative Care and End-of-Life Issues
- Respiratory Support and Mechanisms
- interferon and immune responses
- Influenza Virus Research Studies
- Helminth infection and control
- Viral gastroenteritis research and epidemiology
- Food Safety and Hygiene
Imperial College London
2013-2024
Charles Sturt University
2021
Asthma UK
2010-2019
Lung Institute
2016
National Institutes of Health
2006-2015
West Hertfordshire Hospitals NHS Trust
2010
MRC Laboratory for Molecular Cell Biology
2009
Institute of Molecular and Cell Biology
2006
University of Hertfordshire
1996-2005
St Mary's Hospital
2003
Type I interferons (IFNs) are important for host defense from viral infections, acting to restrict production in infected cells and promote antiviral immune responses. However, the type IFN system has also been associated with severe lung inflammatory disease response respiratory syncytial virus (RSV). Which produce IFNs upon RSV infection how this directs responses virus, potentially results pathological inflammation, is unclear. Here, we show that alveolar macrophages (AMs) major source of...
Infants experiencing severe respiratory syncytial virus (RSV) bronchiolitis have an increased frequency of wheeze and asthma in later childhood. Since most RSV infections occur between the 8th 24th postnatal week, we examined whether age at first infection determines balance cytokine production lung pathology during subsequent rechallenge. Primary newborn mice followed same viral kinetics as adults but was associated with reduced delayed IFN-γ responses. To study rechallenge, were infected 1...
The inflammatory response to lung infections must be tightly regulated, enabling pathogen elimination while maintaining crucial gas exchange. Using recently described "depletion of regulatory T cell" (DEREG) mice, we found that selective depletion cells (Tregs) during acute respiratory syncytial virus (RSV) infection enhanced viral clearance but increased weight loss, local cytokine and chemokine release, T-cell activation cellular influx into the lungs. Conversely, inflammation was...
Abstract Increased stimulation of Th2 cytokines may contribute to the development persistent ocular chlamydial infection, resulting in blinding pathological changes trachoma. Proliferation and cytokine production profiles PBMC response with antigens Chlamydia trachomatis were compared 30 patients severe conjunctival scarring due trachoma age-, sex- location-matched controls. Interferon-gamma (IFN-γ) IL-4 detected at single-cell level by ELISPOT assay. Transcription genes encoding IFN-γ,...
Abstract Eotaxin is a potent eosinophil chemoattractant that acts selectively through CCR3, which expressed on eosinophils, basophils, mast cells, and Th2-type T cells. This arm of the immune system believed to have evolved control helminthic parasites. We hypothesized helminths may employ mechanisms inhibit recruitment, prolong worm survival in host. observed excretory/secretory products hookworm Necator americanus inhibited recruitment vivo response eotaxin, but not leukotriene B4,...
CCL5/RANTES is a key proinflammatory chemokine produced by virus-infected epithelial cells and present in respiratory secretions of asthmatics. To examine the role CCL5 viral lung disease, we measured its production during primary syncytial virus (RSV) infection secondary after sensitizing vaccination that induces Th2-mediated eosinophilia. A first peak mRNA protein was seen at 18 to 24 h RSV infection, before significant lymphocyte recruitment occurred. Treatment vivo with Met-RANTES (a...
Natural killer (NK) cells discern the health of other by recognising balance activating and inhibitory ligands expressed each target cell. However, how integration signals relates to formation NK cell immune synapse remains a central question in our understanding recognition. Here we report that ligation LFA-1 on induced asymmetrical spreading migration. In contrast, receptor NKG2D symmetrical ruffled lamellipodia encompassing dynamic ring f-actin, concurrent with polarization towards "stop"...
Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections. Immunity to RSV initiated upon detection the by pattern recognition receptors, such as RIG-I-like receptors. receptors signal via MAVS induce synthesis proinflammatory mediators, including type I interferons (IFNs), which trigger and shape antiviral responses protect cells from infection. Alveolar macrophages (AMs) are amongst first encounter invading viruses ones producing IFNs. However, it unclear...
Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera patients with CF. In view known relationship ANCA primary vasculitis and their putative pathogenetic role these disorders, we studied presence, specificity isotype clinical associations 66 adult CF patients. None samples had major antigens,...
We report the supramolecular organization of killer Ig–like receptor (KIR) phosphorylation using a technique applicable to imaging any green fluorescent protein–tagged at an intercellular contact or immune synapse. Specifically, we use fluorescence lifetime (FLIM) Förster resonance energy transfer (FRET) between GFP-tagged KIR2DL1 and Cy3-tagged generic anti-phosphotyrosine monoclonal antibody. Visualization KIR in natural (NK) cells contacting target expressing cognate major...
Respiratory syncytial virus (RSV) is a major viral pathogen of infants that also reinfects adults. During RSV infection, inflammatory host cell recruitment to the lung plays central role in determining disease outcome. Chemokines mediate sites inflammation and are influenced by, influence, production cytokines. We therefore compared chemokine mouse model immunopathogenic infection which either Th1 or Th2 immunopathology induced by prior sensitization individual proteins. Chemokine expression...
Abstract Influenza during pregnancy can affect the health of offspring in later life, among which neurocognitive disorders are best described. Here, we investigate whether maternal influenza infection has adverse effects on immune responses offspring. We establish a two-hit mouse model to study effect A virus (first hit) vulnerability heterologous infections (second life. Offspring born infected mothers stunted growth and more vulnerable (influenza B MRSA) than those PBS- or...
C-reactive protein (CRP) is a major acute phase of man, with serum concentrations increasing dramatically following stimulation hepatocytes by inflammatory cytokines. However, the role CRP in inflammation and resistance to infection still poorly understood. Here, specificity binding surface Leishmania donovani, an obligate intracellular parasite mononuclear phagocytes, described. shown bind promastigotes at infectious metacyclic stage development, found normal human serum. The presence on...
BackgroundThe diverse roles of innate immune cells in the pathogenesis asthma remain to be fully defined. Natural killer (NK) are lymphocytes that can regulate adaptive responses. NK activated asthma; however, their role allergic airway inflammation is not understood.ObjectiveWe investigated importance house dust mite (HDM)-triggered pulmonary inflammation. Specifically, we aimed determine major NK-cell activating receptor NKG2D and effector functions mediated by granzyme B.MethodsAllergic...
Infection with respiratory syncytial virus (RSV) in neonatal mice leads to exacerbated disease if are reinfected the same as adults. Both T cells and host major histocompatibility complex genotype contribute this phenomenon, but part played by innate immunity has not been defined. Since macrophages natural killer (NK) play key roles regulating inflammation during RSV infection of adult mice, we studied role these following sensitization/adult reinfection. Compared undergoing primary adults,...
Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that the M3 muscarinic receptor (M3R) plays an important role in adaptive to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired their ability resolve infection with either pathogen. CD4 T cell activation cytokine production reduced mice. Immunity secondary N. was severely impaired, responses accompanied lower numbers of...
CD8 T cells assist in the clearance of respiratory syncytial virus (RSV) infection from lungs. However, disease after RSV is part caused by excessive cell activity, and a balance therefore needed between beneficial harmful cellular immune responses. The chemokine CCL3 (MIP1alpha) produced following broadly chemotactic for both natural killer (NK) cells. We investigated its role disease.CCL3 was biphasically, early (day 1) late 6-7) stages infection. depletion did not alter recruitment to...
ABSTRACT During respiratory-virus infection, excessive lymphocyte activation can cause pathology both in acute infection and exacerbations of chronic respiratory diseases. The costimulatory molecule CD161 is expressed on subsets implicated promoting inflammation, including Th2, Th17, mucosally associated invariant T (MAIT) cells, type 2 innate lymphoid cells. We asked whether the ligand LLT1 could be epithelial cells following as a mechanism by which promote proinflammatory lymphocytes. In...