A5087669504- Vagus Nerve Stimulation Research
- Nicotinic Acetylcholine Receptors Study
- Gut microbiota and health
- Neuropeptides and Animal Physiology
- T-cell and B-cell Immunology
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- Infant Health and Development
- Gastrointestinal motility and disorders
- Helicobacter pylori-related gastroenterology studies
- Immune Cell Function and Interaction
- Heart Rate Variability and Autonomic Control
- Infant Nutrition and Health
- Ion Channels and Receptors
- Circadian rhythm and melatonin
- Neuroendocrine regulation and behavior
- Probiotics and Fermented Foods
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- Tryptophan and brain disorders
- Olfactory and Sensory Function Studies
- Allergic Rhinitis and Sensitization
- Congenital gastrointestinal and neural anomalies
- Neuroscience of respiration and sleep
University of California, Davis
2016-2025
Queen's University
2018
University of California, San Diego
2014-2016
University Health Network
2011-2014
La Jolla Institute for Immunology
2014
Ontario Institute for Cancer Research
2009-2011
Princess Margaret Cancer Centre
2009
University of Calgary
2007-2008
McMaster University
1988-2006
Australian Astronomical Observatory
1988
Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor-α in spleen by a mechanism requiring acetylcholine signaling through α7 nicotinic receptor expressed on cytokine-producing macrophages. Nerve fibers lack enzymatic machinery necessary for production; therefore, how does this neural circuit terminate cholinergic signaling? We identified an...
Appropriate control of immune responses is a critical determinant health. Here, we show that choline acetyltransferase (ChAT) expressed and ACh produced by B cells other have an impact on innate immunity. ChAT expression occurs in mucosal-associated lymph tissue, subsequent to microbial colonization, reduced antibiotic treatment. MyD88-dependent Toll-like receptor up-regulates transient manner. Unlike the previously described CD4(+) T-cell population stimulated norepinephrine release ACh,...
Anxiety, depression, and altered memory are associated with intestinal diseases, including inflammatory bowel disease (IBD). Understanding the link between these behavioral changes IBD is important clinically since concomitant mood disorders often increase a patient's risk of requiring surgery developing secondary functional gastrointestinal diseases. Anxiety-like behavior (light/dark box test) recognition (novel object task) were determined at peak during resolution inflammation in dextran...
The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation the hypothalamic-pituitary-adrenal (HPA) and altered barrier function, dysbiosis, behavioral changes. primary aim this study was determine whether effects on physiology behavior, including anxiety memory, are mediated by adaptive immune system. Furthermore, we wanted treatment with probiotics would normalize these effects. Here...
Effector functions of inflammatory IL-17–producing Th (Th17) cells have been linked to autoimmune diseases such as experimental encephalomyelitis (EAE), a mouse model multiple sclerosis (MS). However, what determines Th17 cell encephalitogenicity is still unresolved. Here, we show that after EAE induction, mice deficient for the NF-κB regulator MALT1 (Malt1–/– mice) exhibit strong lymphocytic infiltration in CNS, but do not develop any clinical signs EAE. Loss Malt1 interfered with...
Although a number of studies have examined the development T-helper cell type 2 (Th2) immunity in different settings, mechanisms underlying initiation this arm adaptive are not well understood. We exploited fact that immunization with antigen plus either nucleotide-binding oligomerization domain-containing proteins 1 (Nod1) or (Nod2) agonists drives Th2 induction to understand how these pattern-recognition receptors mediate systemic immune responses. Here, we show bone-marrow chimeric mice...
•Nucleotide binding oligomerization domain (Nod)-like receptors regulate cognition, anxiety and hypothalamic-pituitary-adrenal axis activation. •Nod-like central peripheral serotonergic biology. are important for maintenance of gastrointestinal physiology. •Intestinal epithelial cell expression Nod1 behaviour.Gut-brain signalling is critical maintaining health homeostasis. Stressful life events can impact gut-brain signalling, leading to altered mood, cognition intestinal dysfunction. In the...
The nervous system plays a profound regulatory role in maintaining appropriate immune responses by signaling to cells. These cells, including B- and T-cells, can further act as intermediary messengers, with subsets of T-cells expressing choline acetyltransferase (ChAT), the enzyme required for acetylcholine (ACh) synthesis. Neural control ACh release from ChAT+ have powerful implications, regulating lymphocyte trafficking, inflammation, prevent death due experimental septic shock. Although...
ABSTRACT The rat tapeworm Hymenolepis diminuta was used to test the hypothesis that helminth infection could modulate murine colitis. Mice were infected with five H. cysticercoids, and colitis evoked via free access 4% (wt/vol) dextran sulfate sodium (DSS)-containing drinking water for 5 days. BALB/c mice either 7 days later exposed DSS (prophylactic strategy) or started on 48 h (treatment strategy). Naive -only - served as controls. On autopsy, colonic segments processed histological...
<i>Helicobacter pylori</i> infects the human gastric mucosa causing a chronic infection that is primary risk factor for cancer development. Recent studies demonstrate <i>H. promotes tolerogenic dendritic cell (DC) development indicating this bacterium evades host immune response. However, signaling pathways involved in modulating DC activation during remain unclear. Here, we report that<i> H. activated signal transducer and activator of transcription 3 (STAT3) pathway...
The regulation of mucosal immune function is critical to host protection from enteric pathogens but incompletely understood. nervous system and the neurotransmitter acetylcholine play an integral part in defense against bacterial pathogens. Here we report that producing-T-cells, as a non-neuronal source ACh, were recruited colon during infection with mouse pathogen Citrobacter rodentium. These ChAT+ T-cells did not exclusively belong one Th subset able produce IFNγ, IL-17A IL-22. To...
Macrophage cytokine production is reflexively mediated by neural circuits. One example the inflammatory reflex, defined electrical signals traveling in vagus nerve and signaling through splenic choline acetyltransferase+ T cells. Lymphocyte acetylcholine ligand for alpha7 nicotinic receptors (α7nAChR) on macrophages that suppress TNF release. Here, we observed stimulation of reflex with a duration 0.1s - 60s significantly reduced systemic release endotoxemia. This suppression was sustained...
Key points It has previously been shown that afferent and efferent vagal nerve stimulation potently inhibits lipopolysaccharide (LPS)‐induced inflammation Our data show inhibition of by but not requires T‐cell derived acetylcholine We neuroimmune circuits require β 2 ‐adrenergic receptor signalling Abstract Chronic due to inappropriate immune cell activation can have significant effects on a variety organ systems, reducing lifespan quality life. As such, highly targeted control is major...
Immune responses in the intestine are intricately balanced to prevent pathogen entry without inducing immunopathology. The nervous system is well established interface with immune fine-tune immunity various organ systems including gastrointestinal tract. Specialized sensory neurons can detect bacteria, bacterial products, and resulting inflammation, coordinate response These release peptide neurotransmitters such as Substance P (SP), induce both neuronal signaling localized nonneuronal...
Abstract Vagus nerve stimulation (VNS) has been shown to limit immune cell activity across several pathologies ranging from sepsis auto-immune diseases. While of vagal efferent neurons previously demonstrated reduce maladaptive host responses during endotoxemia, only selective afferent was able inhibit TLR7-induced macrophage activation and neutrophil recruitment in the lung. These anti-inflammatory actions are facilitated by systemic increases epinephrine, as VNS significantly increased...
Mucosal immune responses to enteric bacterial infections are highly coordinated processes that orchestrate host protection while minimizing the potential for immune-triggered pathology. In intestinal tract, bidirectional communication occurs between nervous and systems affect local by modulating activity of resident recruited cells, indirectly on supporting stromal cells. These neuroimmune signaling pathways alter defense have focused specialized sensory innervation unique neurotransmitters...
BackgroundIntestinal bacterial infections are a major cause of morbidity and mortality, especially in neonates. Therefore, the aims this study were to characterize Citrobacter rodentium infection neonatal mice determine role played by specific probiotics ameliorating disease severity MethodsInfection C57BL/6 with C. was performed at postnatal day 14. A subset pretreated orally either mixture Lactobacillus rhamnosus helveticus or placebo, starting 7 days. To effects B T cells, rag1−/− JH−/−...
Significance More than 1 million people worldwide suffer from the debilitating neurological disorder multiple sclerosis (MS). The initiation of MS is associated with sustained inflammation and an autoimmune T-cell response targeting central nervous system. activities Th1 Th17 effector T cells, which are main pathogenic drivers MS, balanced by regulatory dampen mitigate disease. Our study describes important role for surface receptor Toso in balancing these subsets controlling inflammation....