- Prion Diseases and Protein Misfolding
- Immune Cell Function and Interaction
- Trace Elements in Health
- Immunotherapy and Immune Responses
- Neuroinflammation and Neurodegeneration Mechanisms
- Trypanosoma species research and implications
- Immune Response and Inflammation
- Immune cells in cancer
- T-cell and B-cell Immunology
- Neurological diseases and metabolism
- HIV Research and Treatment
- RNA regulation and disease
- Gut microbiota and health
- Research on Leishmaniasis Studies
- Reproductive System and Pregnancy
- Alzheimer's disease research and treatments
- Viral gastroenteritis research and epidemiology
- RNA Interference and Gene Delivery
- Animal Disease Management and Epidemiology
- IL-33, ST2, and ILC Pathways
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- Amino Acid Enzymes and Metabolism
- Digestive system and related health
- Probiotics and Fermented Foods
Roslin Institute
2016-2025
University of Edinburgh
2016-2025
University of Glasgow
2023
Queen Mary University of London
2023
University of Manchester
2023
Weatherford College
2023
National Institute of Biomedical Research
2023
Wellcome Centre for Molecular Parasitology
2023
University of Strathclyde
2023
University of Kinshasa
2023
The specialisation of mammalian cells in time and space requires genes associated with specific pathways functions to be co-ordinately expressed. Here we have combined a large number publically available microarray datasets derived from human primary analysed correlation graphs these data. Using the network analysis tool BioLayout Express3D identify robust co-associations expressed wide variety cell lineages. We discuss biological significance associations, particular coexpression key...
Abstract The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. mammalian Csf1r locus contains a highly conserved super-enhancer, fms -intronic regulatory element (FIRE). Here we show that genomic deletion FIRE in mice selectively impacts CSF1R expression tissue development specific tissues. Deletion ablates murine embryonic stem cells. ΔFIRE/ΔFIRE lack macrophages embryo, brain microglia...
Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context this response can be beneficial for host: influenza A virus infection–induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite ubiquity their role both health little is known about mechanisms by which inflammation able convert peripheral...
Abstract Colony-stimulating factor 1 (CSF1) controls the growth and differentiation of macrophages.CSF1R signaling has been implicated in maintenance intestinal stem cell niche Paneth cells, but evidence expression CSF1R within crypt is equivocal. Here we show that CSF1R-dependent macrophages influence epithelial homeostasis. In lamina propria mRNA restricted to which are intimately associated with epithelium, undetectable cells. Macrophage ablation following blockade affects leads a...
Microglia are brain-resident macrophages that contribute to central nervous system (CNS) development, maturation, and preservation. Here, we examine the consequences of permanent microglial deficiencies on brain aging using Csf1r
Bovine spongiform encephalopathy, variant Creutzfeldt-Jakob disease (vCJD) and possibly also sheep scrapie are orally acquired transmissible encephalopathies (TSEs). TSE agents usually replicate in lymphoid tissues before they spread into the central nervous system. In mouse models PrP(c)-expressing follicular dendritic cells (FDCs) resident germinal centres essential for replication, their absence neuroinvasion is impaired. Disease-associated forms of PrP (PrP(Sc)), a biochemical marker...
Intestinal immune homeostasis is dependent upon tightly regulated and dynamic host interactions with the commensal microbiota. Immunoglobulin A (IgA) produced by mucosal B cells dictates composition of bacteria residing within intestine. While emerging evidence suggests majority IgA innately may be polyreactive, mucosal-dwelling species can also elicit via T cell–dependent mechanisms. However, mechanisms that modulate magnitude quality responses remain incompletely understood. Here we...
After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic (FDCs) before spreading the nervous system. How actually initially acquired from gut lumen is not known. Using high-resolution immunofluorescence cryo-immunogold electron microscopy, we report trafficking of prion protein (PrP) toward wild-type PrP-deficient mice. PrP was transiently detectable at 1 day post feeding (dpf) within large multivesicular LAMP1-positive...
We have produced Csf1r-deficient rats by homologous recombination in embryonic stem cells. Consistent with the role of Csf1r macrophage differentiation, there was a loss peripheral blood monocytes, microglia brain, epidermal Langerhans cells, splenic marginal zone macrophages, bone-associated macrophages and osteoclasts, peritoneal macrophages. Macrophages red pulp, liver, lung, gut were less affected. The pleiotropic impacts on development multiple organ systems distinct from those reported...
Abstract We investigated the role of CSF1R signaling in adult mice using prolonged treatment with anti-CSF1R antibody. Mutation CSF1 gene op/op mouse produces numerous developmental abnormalities. has an even more penetrant phenotype, including perinatal lethality, because existence a second ligand, IL-34. These effects on development provide limited insight into functions homeostasis. The carcass weight and several organs (spleen, kidney, liver) were reduced treated mice, but overall body...
Immunity decreases with age, which leads to reactivation of varicella zoster virus (VZV). In human subjects age-associated immune changes are usually measured in blood leukocytes; however, this might not reflect alterations tissue-specific immunity.We used a VZV antigen challenge system the skin investigate mechanisms involved decreased response during aging.We assessed cutaneous immunity based on extent erythema and induration after intradermal injection. We also performed histology...
Abstract Mammalian three-dimensional (3D) enteroids mirror in vivo intestinal organisation and are powerful tools to investigate cell biology host–pathogen interactions. We have developed complex multilobulated 3D chicken from embryonic villi adult crypts. These avian develop optimally suspension without the structural support required produce mammalian enteroids, resulting an inside-out enteroid conformation with media-facing apical brush borders. Histological transcriptional analyses show...
ABSTRACT Transmissible spongiform encephalopathies (TSEs) may be acquired peripherally, in which case infectivity usually accumulates lymphoid tissues before dissemination to the nervous system. Studies of mouse scrapie models have shown that mature follicular dendritic cells (FDCs), expressing host prion protein (PrP c ), are critical for replication infection and subsequent neuroinvasion. Since FDCs require lymphotoxin signals from B lymphocytes maintain their differentiated state,...