A5023240519- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Immune cells in cancer
- Inflammasome and immune disorders
- Immunotherapy and Immune Responses
- interferon and immune responses
- IL-33, ST2, and ILC Pathways
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- RNA Research and Splicing
- Animal Genetics and Reproduction
- Phagocytosis and Immune Regulation
- NF-κB Signaling Pathways
- Viral Infections and Vectors
- Cytokine Signaling Pathways and Interactions
- Neonatal Respiratory Health Research
- Conducting polymers and applications
- Extracellular vesicles in disease
- Cell Adhesion Molecules Research
- Inflammatory Bowel Disease
- Chemokine receptors and signaling
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
Translational Research Institute
2019-2024
The University of Queensland
2005-2024
Queensland University of Technology
2024
Malaghan Institute of Medical Research
2022-2023
Roslin Institute
2009-2013
University of Edinburgh
2009-2013
University of Glasgow
2009-2010
Complications arising from dengue virus infection include potentially fatal vascular leak, and severe disease has been linked with excessive immune cell activation. An understanding of the triggers this activation is critical for development appropriately targeted control strategies. We show here that secreted form nonstructural protein 1 (NS1) a pathogen-associated molecular pattern (PAMP). Highly purified NS1 devoid bacterial endotoxin activity directly activated mouse macrophages human...
Macrophages (Mphis) in the large intestine are crucial effectors of inflammatory bowel disease, but also essential for homeostasis. It is unclear if these reflect separate populations Ms or resident change during inflammation. In this study, we identify two subsets colonic mice, whose proportions differ healthy and inflamed intestine. Under resting conditions, most F4/80+ TLR- CCR2- CX3CR1hi do not produce TNF-alpha response to stimulation. The lack TLR expression stable, affects all TLRs,...
Macrophages are involved in many aspects of development, host defense, pathology, and homeostasis. Their normal differentiation, proliferation, survival controlled by CSF-1 via the activation CSF1R. A recently discovered cytokine, IL-34, was shown to bind same receptor humans. Chicken is a widely used model organism developmental biology, but factors that control avian myelopoiesis have not been identified previously. The CSF-1, CSF1R genes chicken zebra finch were from respective...
Mouse bone marrow-derived macrophages (BMDM) grown in M-CSF (CSF-1) have been used widely studies of macrophage biology and the response to TLR agonists. We investigated whether similar cells could be derived from domestic pig using human rCSF-1 porcine might represent a better model biology. Cultivation marrow for 5-7 d presence generated pure population BMDM that expressed usual markers (CD14, CD16, CD172a), were potent phagocytic cells, produced TNF LPS. Pig had stored frozen thawed so...
Abstract Inflammasomes are large protein complexes induced by a wide range of microbial, stress, and environmental stimuli that function to induce cell death inflammatory cytokine processing. Formation an inflammasome involves dramatic relocalization the adapter apoptosis-associated speck-like containing caspase recruitment domain (ASC) into single speck. We have developed flow cytometric assay for formation, time flight evaluation, which detects change in ASC distribution within cell. The...
Abstract Macrophages and B cells are activated by unmethylated CpG-containing sequences in bacterial DNA. The lack of activity self DNA has generally been attributed to CpG suppression methylation, although the role methylation is doubt. frequency mouse genome 12.5% Escherichia coli, with occurring at ∼3% E. coli. This alone insufficient explain inactivity DNA; vertebrate was inactive 100 μg/ml, 3000 times concentration which coli observed. We sought resolve why does not activate...
Abstract We report in this study that activation of the JNK by growth factor, CSF-1 is critical for macrophage development, proliferation, and survival. Inhibition with two distinct classes inhibitors, pharmacological agent SP600125, or peptide D-JNKI1 resulted cell cycle inhibition an arrest at G2/M transition subsequent apoptosis. decreased expression CSF-1R (c-fms) Bcl-xL mRNA mature macrophages repressed CSF-1-dependent differentiation bone marrow cells to macrophages. Macrophage...
Human and mouse monocyte can be divided into two different subpopulations based on surface marker expression: CD14/16 Ly6C/CX3CR1, respectively. Monocyte in the pig were identified reciprocal expression of CD14 scavenger receptor CD163. The populations, CD14(hi)-CD163(low) CD14(low)-CD163(hi), show approximately equal abundance steady-state. Culture PBMCs CSF1 indicates that populations are a maturation series controlled by this growth factor. Gene was profiled using newly developed...
Mouse p202 containing two hemopoietic expression, interferon inducibility, nuclear localization (HIN) domains antagonizes AIM2 inflammasome signaling and potentially modifies lupus susceptibility. We found that only HIN1 of binds double-stranded DNA (dsDNA), while HIN2 forms a homotetramer. Crystal structures revealed dsDNA is bound on face opposite the site used in IFI16. The structure dimer dimers, analogous to binding being dimerization interface. Electron microscopy imaging showed...
Abstract Macrophages respond to unmethylated CpG motifs present in nonmammalian DNA. Stabilized phosphorothioate-modified oligodeoxynucleotides (PS-ODN) containing form the basis of immunotherapeutic agents. In this study, we show that PS-ODN do not perfectly mimic native DNA activation macrophages. CpG-containing were active at 10- 100-fold lower concentrations than corresponding phosphodiester ODN maintenance cell viability absence CSF-1, induction NO production, and IL-12 promoter. These...
During bacterial infections, the balance between resolution of infection and development sepsis is dependent upon macrophage response to products. We show that priming murine bone marrow-derived macrophages (BMMs) with CSF-1 differentially regulates two such stimuli, LPS immunostimulatory (CpG) DNA. pretreatment enhanced IL-6, IL-12, TNF-alpha production in but suppressed same CpG also regulated cytokine gene expression DNA LPS; DNA-induced IL-12 p40, p35, mRNAs were all by pretreatment....
Abstract Background The draft genome of the domestic pig (Sus scrofa) has recently been published permitting refined analysis transcriptome. Pig breeds have reported to differ in their resistance infectious disease. In this study we examine whether there are corresponding differences gene expression innate immune cells Results We demonstrate that macrophages can be harvested from three different compartments (lungs, blood and bone-marrow), cryopreserved subsequently recovered differentiated...
Macrophage Colony Stimulating Factor (CSF-1) controls the survival, differentiation and proliferation of cells mononuclear phagocyte system. A second ligand for CSF-1R, Interleukin 34 (IL-34), has been described, but its physiological role is not yet known. The domestic pig provides an alternative to traditional rodent models evaluating potential therapeutic applications CSF-1R agonists antagonists. To enable such studies, we cloned expressed active CSF-1. provide a bioassay, was in...
ABSTRACT The mosquito-borne West Nile virus (WNV) is responsible for outbreaks of viral encephalitis in humans, horses, and birds, with particularly virulent strains causing recent disease eastern Europe, the Middle East, North America, Australia. Previous studies have phylogenetically separated WNV into two main genetic lineages (I II) containing associated neurological disease. Several WNV-like clustering outside these been identified form an additional five proposed lineages. However,...
Unmethylated CpG motifs within bacterial DNA constitute a pathogen-associated molecular pattern recognized by the innate immune system. Many of immunomodulatory functions can be ascribed to ability activate macrophages and dendritic cells. Here we show stimulatory DNA, like LPS, caused growth arrest murine bone marrow-derived proliferating in CSF-1. Stimulatory selective down-modulation CSF-1 receptor surface expression. Flow cytometric analysis CSF-1-deprived revealed that contrast...
Abstract Bacterial CpG-containing (CpG) DNA promotes survival of murine macrophages and triggers production proinflammatory mediators. The CpG DNA-induced inflammatory response is mediated via TLR9, whereas a recent study reported that activation the Akt prosurvival pathway occurs DNA-dependent protein kinase (DNA-PK) independently TLR9. We show, in this study, bone marrow-derived (BMM) triggered by phosphodiester oligodeoxynucleotides or phosphorothioate was completely dependent on In...
Proinflammatory CC chemokines control leukocyte recruitment and function during inflammation by engaging chemokine receptors expressed on circulating leukocytes. The D6 receptor can bind several of these chemokines, but appears unable to couple signal transduction pathways or direct cell migration. Instead, has been proposed act as a scavenger, removing proinflammatory dampen responses. In this study, we have examined the role in colon using dextran sodium sulfate-induced model colitis. We...