A5003604608- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Cell Adhesion Molecules Research
- Lipid Membrane Structure and Behavior
- Immune Cell Function and Interaction
- Adenosine and Purinergic Signaling
- Animal Virus Infections Studies
- Erythrocyte Function and Pathophysiology
- interferon and immune responses
- Redox biology and oxidative stress
- Neonatal Respiratory Health Research
- Phagocytosis and Immune Regulation
- Parasitic Infections and Diagnostics
- Calcium signaling and nucleotide metabolism
- Gut microbiota and health
- Tuberculosis Research and Epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Sphingolipid Metabolism and Signaling
- Mycobacterium research and diagnosis
University of Calgary
2016-2025
Institute of Human Sciences
2024
Office of International Affairs
2024
Yale University
2024
Tehran University of Medical Sciences
2023
Cornell University
2005-2014
Matrix Research (United States)
2014
Shandong Agricultural University
2011
New York State College of Veterinary Medicine
2006-2010
University of Veterinary Medicine
2010
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is reaching epidemic proportions causing morbidity, mortality, and chronic disease due to relapses, suggesting an intracellular reservoir. Using spinning-disk confocal intravital microscopy track MRSA-GFP in vivo, we identified that within minutes after intravenous infection MRSA primarily sequestered killed by intravascular Kupffer cells (KCs) the liver. However, a minority of Staphylococci overcome KC's antimicrobial defenses....
ABSTRACT The mucosa-associated microflora is increasingly considered to play a pivotal role in the pathogenesis of inflammatory bowel disease. This study explored possibility that an abnormal mucosal flora involved etiopathogenesis granulomatous colitis Boxer dogs (GCB). Colonic biopsy samples from affected ( n = 13) and controls 38) were examined by fluorescent situ hybridization (FISH) with eubacterial 16S rRNA probe. Culture, ribosomal DNA sequencing, histochemistry used guide subsequent...
Professional phagocytes function at the hinge of innate and acquired immune responses by internalizing particulate material that is digested sampled within phagosome cell. Despite intense interest, assays to measure maturation remain insensitive few in number. In this current study, we describe three novel quantify important biological properties as it matures. One assay exploits fluorescence resonance energy transfer mixing phagocytosed particles carrying a donor fluor with an acceptor...
Epithelial permeability is often increased in inflammatory bowel diseases. We hypothesized that perturbed mitochondrial function would cause barrier dysfunction and hence epithelial mitochondria could be targeted to treat intestinal inflammation. Mitochondrial was induced human colon-derived cell lines or colonic biopsy specimens using dinitrophenol, assessed by transepithelial flux of Escherichia coli with without mitochondria-targeted antioxidant (MTA) cotreatment. The impact antioxidants...
The phagosomal lumen in macrophages is the site of numerous interacting chemistries that mediate microbial killing, macromolecular degradation, and antigen processing. Using a non-hypothesis-based screen to explore interconnectivity functions, we found NADPH oxidase (NOX2) negatively regulates levels proteolysis within maturing phagosome macrophages. Unlike NOX2 mechanism proteolytic control reported dendritic cells, this phenomenon independent changes lumenal pH also hydrolase delivery...
The phagosome is key to most macrophage functions. It the site of degradation particulate material, bacterial killing and generation peptides for antigen presentation. Despite its role at fulcrum innate acquired immune systems, little known about physiology this organelle in activated macrophages. In study, we utilize fluorometric techniques characterize functional alterations lumenal environment maturing following stimulation macrophages with interferon‐γ and/or lipopolysaccharide. addition...
Giardia duodenalis (syn. G. intestinalis, lamblia) infections are a leading cause of waterborne diarrheal disease that can also result in the development postinfectious functional gastrointestinal disorders via mechanisms remain unclear. Parasite numbers exceed 10(6) trophozoites per centimeter gut at height an infection. Yet intestinal mucosa duodenalis-infected individuals is devoid signs overt inflammation. occur concurrently with other proinflammatory pathogens. Little known whether and...
Intracellular chloride channel protein 1 (CLIC1) is a 241 amino acid of the glutathione S transferase fold family with redox- and pH-dependent membrane association ion activity. Whilst CLIC proteins are evolutionarily conserved in Metazoa, indicating an important role, little known about their biology. CLIC1 was first cloned on basis increased expression activated macrophages. We therefore examined its subcellular localisation murine peritoneal macrophages by immunofluorescence confocal...
The chemistries within phagosomes of APCs mediate microbial destruction as well generate peptides for presentation on MHC class II. antimicrobial effector NADPH oxidase (NOX2), which generates superoxide maturing phagosomes, has also been shown to regulate activities cysteine cathepsins through modulation the lumenal redox potential. Using real-time analyses microenvironmental parameters, in conjunction with hydrolysis pattern assessment phagocytosed proteins, we demonstrated that NOX2...
Although it is known that lysosomal cysteine cathepsins require a reducing environment for optimal activity, not firmly established how these enzymes are maintained in their reduced-active state the acidic and occasionally oxidative within phagosomes lysosomes. γ-Interferon-inducible thiol reductase (GILT) has been only enzyme described endosomes, lysosomes, with potential to catalyze reduction of cathepsins. Our goal current study was assess effect GILT on major phagosomal functions an...
Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound virus therapies also modulate host immune responses in ways we hypothesized would complement one another promoting anticancer T-cell immunity. We show that synergize driving CD8
Generation of an oxidative burst within the phagosomes neutrophils, dendritic cells and macrophages is essential component innate immune system. To examine kinetics in macrophage phagosome, we developed two new assays using beads coated with oxidation-sensitive fluorochromes.These permitted quantification temporal resolution phagosome. The phagosomal short lived,with oxidation bead-associated substrates reaching maximal activity 30 min following phagocytosis.Additionally, extent rate...
Generation of an oxidative burst within the phagosomes neutrophils, dendritic cells and macrophages is essential component innate immune system. To examine kinetics in macrophage phagosome, we developed two new assays using beads coated with oxidation‐sensitive fluorochromes. These permitted quantification temporal resolution phagosome. The phagosomal short lived, oxidation bead‐associated substrates reaching maximal activity 30 min following phagocytosis. Additionally, extent rate substrate...
Giardia duodenalis infections are among the most common causes of waterborne diarrhoeal disease worldwide. At height infection, G. trophozoites induce multiple pathophysiological processes within intestinal epithelial cells that contribute to development disease. To date, our understanding in giardiasis remains incompletely understood. The present study reveals a previously unappreciated role for cathepsin cysteine proteases occur during giardiasis. Experiments first established indeed...
Hypomethylation of the cathepsin Z locus has been proposed as an epigenetic risk factor for multiple sclerosis (MS). Cathepsin is a unique lysosomal cysteine expressed primarily by antigen presenting cells. While expression associated with neuroinflammatory disorders, role in mediating neuroinflammation not previously established. Experimental autoimmune encephalomyelitis (EAE) was induced both wildtype mice and deficient Z. The effects Z-deficiency on processing presentation autoantigen...
Recognition of pathogen-or-damage-associated molecular patterns is critical to inflammation. However, most exist within intact microbes/cells and are typically part non-diffusible, stable macromolecules that not optimally immunostimulatory or available for immune detection. Partial digestion following phagocytosis potentially generates new diffusible patterns, however, our current understanding phagosomal biology would have these molecules sequestered destroyed phagolysosomes. Here, we show...
Abstract Adenovirus is a nonenveloped dsDNA virus that activates intracellular innate immune pathways. In vivo, adenovirus-immunized mice displayed an enhanced response and diminished virus-mediated gene delivery following challenge with the adenovirus vector AdLacZ suggesting antiviral Abs modulate viral interactions cells. Under naive serum conditions in vitro, binding internalization macrophages subsequent activation of mechanisms were inefficient. contrast to neutralizing effect observed...
Conventional dendritic cells (cDCs) generate protective cytotoxic T lymphocyte (CTL) responses against extracellular pathogens and tumors. This is achieved through a process known as cross-presentation (XP), and, despite its biological importance, the mechanism(s) driving XP remains unclear. Here, we show that cDC-specific pore-forming protein called apolipoprotein L 7C (APOL7C) up-regulated in response to innate immune stimuli recruited phagosomes. Association of APOL7C with phagosomes led...
Macrophages play a pivotal role in clearing debris and microbes from the microenvironment via phagocytosis orchestrating local inflammation. While mostly understood to be through synthesis secretion of soluble mediators such as cytokines eicosanoids, it has been recently proposed that macrophages can release previously phagocytosed processed PAMPs DAMPs into process termed eructophagy, these, turn, activate vicinal leukocytes. Additionally, commonly observed physically interact with other...