A5022826302- Respiratory viral infections research
- Neonatal Respiratory Health Research
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Pediatric health and respiratory diseases
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- interferon and immune responses
- Immunotherapy and Immune Responses
- Immune cells in cancer
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Cervical Cancer and HPV Research
- Respiratory Support and Mechanisms
- Congenital Diaphragmatic Hernia Studies
- IL-33, ST2, and ILC Pathways
- Salmonella and Campylobacter epidemiology
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Escherichia coli research studies
- Cytokine Signaling Pathways and Interactions
- Asthma and respiratory diseases
- Pneumonia and Respiratory Infections
- RNA Research and Splicing
- Molecular Biology Techniques and Applications
Imperial College London
2015-2024
University of Lusaka
2024
Lung Institute
2016-2023
St Mary's Hospital
2019
St. Mary's Hospital
2019
King's College London
2017
Lund University
2000-2015
Asthma UK
2012-2013
Medical Research Council
2013
Dynavax Technologies (United States)
2013
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...
The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, whom 57% became infected. Mucosal neutrophil activation before was highly predictive symptomatic RSV disease. This associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed IL-17- tumor necrosis factor-related pathways. Vulnerability not baseline...
CD1d-restricted natural killer T (NKT) cells are a subset of regulatory that react with glycolipid antigens. Although preclinical studies have effectively targeted NKT for immunotherapy, little is known regarding the early in vivo response these to antigenic stimulation. We analyzed antigens and bacterial infection by using specific reagents tracking cells. Our results demonstrate dramatic expansion surface phenotype alterations after cell activation α-galactosylceramide. In addition, we...
The in vivo administration of certain monoclonal antibodies (mAbs) against the adhesion receptor, CD44, into normal mice induces both a modulation CD44 from surface peripheral lymphocytes, and concomitant increase amount soluble serum. CD44-negative lymphocytes isolated anti-CD44-treated exhibit homing patterns upon adoptive transfer, are capable reexpressing activation. treatment haptensensitized with anti-CD44 mAb inhibits their ability to mount cutaneous delayed-type hypersensitivity...
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 Regulatory CD4 + T cells have been shown to be important in limiting immune responses, but their role respiratory viral infections has received little attention. Here we observed that following syncytial virus (RSV) infection, Foxp3 CD25 natural regulatory T-cell numbers increased the bronchoalveolar lavage fluid, lung, mediastinal lymph nodes, and spleen. The depletion of prior RSV infection led enhanced weight loss with delayed recovery was surprisingly accompanied by activated...
Type I interferons (IFNs) are produced early upon virus infection and signal through the alpha/beta interferon (IFN-α/β) receptor (IFNAR) to induce genes that encode proteins important for limiting viral replication directing immune responses. To investigate extent which type IFNs play a role in local regulation of inflammation airways, we examined their importance lung responses with respiratory syncytial (RSV). IFNAR1-deficient (IFNAR1(-/-)) mice displayed increased load weight loss during...
Interleukin (IL-) 10 is a pleiotropic cytokine with broad immunosuppressive functions, particularly at mucosal sites such as the intestine and lung. Here we demonstrate that infection of BALB/c mice respiratory syncytial virus (RSV) induced IL-10 production by CD4+ CD8+ T cells in airways later time points (e.g. day 8); proportion these also co-produced IFN-γ. Furthermore, RSV IL-10−/− resulted more severe disease enhanced weight loss, delayed recovery greater cell infiltration tract without...
ABSTRACT During viral infection, inflammation and recovery are tightly controlled by competing proinflammatory regulatory immune pathways. Respiratory syncytial virus (RSV) is the leading global cause of infantile bronchiolitis, which associated with recurrent wheeze asthma diagnosis in later life. Th2-driven disease has been well described under some conditions for RSV-infected mice. In present studies, we used Foxp3 DTR mice (which allow specific conditional depletion + T cells) to...
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...
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...
Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections, especially in infants. Lung neutrophilia hallmark RSV disease but the mechanism by which neutrophils are recruited and activated unclear. Here, we investigate innate immune signaling pathways underlying neutrophil recruitment activation RSV-infected mice. We show that MyD88/TRIF essential for lung while MAVS signaling, to type I IFN production, necessary activation. Consistent with notion,...
To be effective, RNA vaccines require both
To date, the entry pathway and replication mechanisms for members of family Bunyaviridae, especially Crimean-Congo hemorrhagic fever virus (CCHFV), are poorly understood. Considering severity disease widespread geographical occurrence CCHFV, investigating viral is great value development antivirals. In this study, we have shown that knockdown clathrin by small interfering RNA significantly reduced CCHFV nucleocapsid protein levels, suggesting utilizes clathrin-dependent endocytosis....
We defined the function of type I interferons (IFNs) in defense against reovirus strain 1 Lang (T1L), which is a double-stranded RNA virus that infects Peyer's patches (PPs) after peroral inoculation mice. T1L induced expression mRNA for IFN-α, IFN-β, and Mx-1 PPs caused localized intestinal infection was cleared 10 d. In contrast, produced fatal systemic IFNαR1 knockout (KO) mice with extensive cell loss lymphoid tissues necrosis mucosa. Studies bone-marrow chimeric indicated an essential...
Human trials of formaldehyde-inactivated respiratory syncytial virus (FI-RSV) vaccine in 1966–1967 caused disastrous worsening disease and death infants during subsequent natural (RSV) infection. The reasons behind vaccine-induced augmentation are only partially understood, fear continues to hold back development. We now show that mice vaccinated with FI-RSV enhanced local recruitment conventional CD4 + T cells accompanied by a profound loss regulatory (Tregs) the airways. This Tregs was so...
Most adenoviruses bind to the coxsackie- and adenovirus receptor (CAR). Surprisingly, CAR is not expressed apically on polarized cells thus easily available viruses. Consequently, alternative mechanisms for entry of coxsackievirus into have been suggested. We found that tear fluid promotes infection, we identified human lactoferrin (HLf) as component responsible this effect. HLf alone was promote binding epithelial in a dose-dependent manner also infection by adenovirus. gene delivery from...