Severe, but not moderate asthmatics share blood transcriptomic changes with post-traumatic stress disorder and depression.

Asthma, an inflammatory disorder of the airways, is one of the most common chronic illnesses worldwide and is associated with significant morbidity. There is growing recognition of an association between asthma and mood disorders including post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). Although there are several hypotheses regarding the relationship between asthma and mental health, there is little understanding of underlying mechanisms and causality.

Effects of Two Distinct Psychoactive Microbes, JB-1 and 6475, on Circulating and Hippocampal mRNA in Male Mice.

Discovery of the microbiota-gut-brain axis has led to proposed microbe-based therapeutic strategies in mental health, including the use of mood-altering bacterial species, termed psychobiotics. However, we still have limited understanding of the key signaling pathways engaged by specific organisms in modulating brain function, and evidence suggests that bacteria with broadly similar neuroactive and immunomodulatory actions can drive different behavioral outcomes. We sought to identify pathways distinguishing two psychoactive bacterial strains that seemingly engage similar gut-brain signaling pathways but have distinct effects on behaviour.

Colonic Motility and Jejunal Vagal Afferent Firing Rates Are Decreased in Aged Adult Male Mice and Can Be Restored by an Aminosterol.

There is a general decline in gastrointestinal function in old age including decreased intestinal motility, sensory signaling, and afferent sensitivity. There is also increased prevalence of significant constipation in aged populations. We hypothesized this may be linked to reduced colonic motility and alterations in vagal-gut-brain sensory signaling.

Mast Cells in Neuroimmune Interactions.

A major aspect of the regulatory function of mast cells appears to be their role as intermediaries between the nervous and immune systems. Mast cells are activated by neurotransmitters allowing neural control of innate and adaptive immunity. Conversely, mast cells secrete mediators including neurotransmitters and neurotrophic factors that directly influence nerves, causing acute activation and/or long-lasting changes in excitability and phenotype.

Vitamin D-deficiency induces eosinophil spontaneous activation.

Eosinophils (Eo) play a critical role in immunity and immune inflammation. The maintenance of Eo homeostasis is not fully understood yet. Vitamin D (VitD) is involved in the regulation of a large number of biochemical reactions.

Targeting histone-acetyltransferase Tat-interactive protein 60 inhibits intestinal allergy.

Background: The overproduction of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone-acetyltransferase (HAT) activities are required in gene transcription of a large number of molecules in the immune system of the body.

Objectives: This study tests a hypothesis that HAT Tat-interactive protein 60 (Tip60) plays an important role in the initiation of IgE-mediated allergy.

Vitamin D regulates immunoglobulin mucin domain molecule-4 expression in dendritic cells.

Background: Dendritic cell (DC)-derived immunoglobulin domain molecule (TIM)4 plays a critical role in the initiation of T helper (Th)2 polarization. Vitamin D (VitD) involves the regulation of a number of immune responses.

Objectives: This study tests a hypothesis that VitD regulates TIM4 expression in DCs.

Oral treatment with Lactobacillus rhamnosus attenuates behavioural deficits and immune changes in chronic social stress.

Background: Stress-related disorders involve systemic alterations, including disruption of the intestinal microbial community. Given the putative connections between the microbiota, immunity, neural function, and behaviour, we investigated the potential for microbe-induced gut-to-brain signalling to modulate the impact of stress on host behaviour and immunoregulation.

Methods: Male C57BL/6 mice treated orally over 28 days with either Lactobacillus rhamnosus (JB-1) ™ or vehicle were subjected to chronic social defeat and assessed for alterations in behaviour and immune cell phenotype.

Superior Cervical Ganglia Neurons Induce Foxp3+ Regulatory T Cells via Calcitonin Gene-Related Peptide.

The nervous and immune systems communicate bidirectionally, utilizing diverse molecular signals including cytokines and neurotransmitters to provide an integrated response to changes in the body's internal and external environment. Although, neuro-immune interactions are becoming better understood under inflammatory circumstances and it has been evidenced that interaction between neurons and T cells results in the conversion of encephalitogenic T cells to T regulatory cells, relatively little is known about the communication between neurons and naïve T cells. Here, we demonstrate that following co-culture of naïve CD4+ T cells with superior cervical ganglion neurons, the percentage of Foxp3 expressing CD4+CD25+ cells significantly increased.

Thrombospondin-1 (TSP1)-producing B cells restore antigen (Ag)-specific immune tolerance in an allergic environment.

Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation.

The parasympathetic nervous system as a regulator of mast cell function.

Often considered as the archetype of neuroimmune communication, much of our understanding of the bidirectional relationship between the nervous and immune systems has come from the study of mast cell-nerve interaction. Mast cells play a role in resistance to infection and are extensively involved in inflammation and subsequent tissue repair. Thus, the relationship between mast cells and neurons enables the involvement of peripheral and central nervous systems in the regulation of host defense mechanisms and inflammation.

Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity.

Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping.

Effects of complete vagotomy and blockage of cell adhesion molecules on interferon-α induced behavioral changes in mice.

Objectives: Sickness behavior and chronic immune diseases are frequently associated with depressive symptomatology. In addition, immune activation by single cytokine therapies, such as treatment of malignancies and hepatitis C with interferon-alpha (IFN-α) often induces significant changes in emotional reactivity and affect. However, underlying pathogenic mechanisms of cytokine-induced brain dysfunction largely remain unknown.

A Lactobacillus rhamnosus strain induces a heme oxygenase dependent increase in Foxp3+ regulatory T cells.

We investigated the consequences of feeding with a Lactobacillus species on the immune environment in GALT, and the role of dendritic cells and heme oxygenase-1 in mediating these responses. Feeding with a specific strain of Lactobacillus rhamnosus induced a significant increase in CD4+CD25+Foxp3+ functional regulatory T cells in GALT. This increase was greatest in the mesenteric lymph nodes and associated with a marked decrease in TNF and IFNγ production.

Altered olfactory function in the MRL model of CNS lupus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that damages several bodily systems, including the CNS. Brain atrophy and diverse neuropsychiatric manifestations are common and serious complications of SLE. Recently, it has been reported that many patients with CNS involvement also present with olfactory deficits of unknown etiology.

The mast cell-nerve functional unit: a key component of physiologic and pathophysiologic responses.

A key characteristic of mast cells appears to be an ability to span the division between nervous and immune system. Indeed, much of our understanding of the bi-directional relationship between the nervous and immune systems has come from the study of mast cell-nerve interaction. Although differences in species have been reported, morphologic as well as functional associations between mast cell and nerves are found in most tissues in many mammalian species, including humans.

Voices from within: gut microbes and the CNS.

Recent advances in research have greatly increased our understanding of the importance of the gut microbiota. Bacterial colonization of the intestine is critical to the normal development of many aspects of physiology such as the immune and endocrine systems. It is emerging that the influence of the gut microbiota also extends to modulation of host neural development.

Immunomodulation by commensal and probiotic bacteria.

Over the past decade there has been an increasing awareness of the role played by commensal bacteria in modulating mucosal immune responses and as a consequence there is now great interest in the therapeutic potential of probiotics and other bacteria based strategies for a range of immune disorders. Here we review current understanding of the mechanisms underlying the immunomodulatory actions of commensal and probiotic bacteria and probiotic organisms. We discuss prominent cell types involved in transducing signals from these bacteria, including epithelial cells, dendritic cells and T regulatory cells.

The vagus nerve modulates CD4+ T cell activity.

The vagus nerve has a counter-inflammatory role in a number of model systems. While the majority of these anti-inflammatory effects have been ascribed to the activation of nicotinic receptors on macrophages, little is known about the role of the vagus in modulating the activity of other cells involved in inflammatory responses. Here, we demonstrate that following subdiaphragmatic vagotomy of mice CD4(+) T cells from the spleen proliferated at a higher rate and produced more pro-inflammatory cytokines, including TNF and IFN-gamma, upon in vitro stimulation.

Intrathecal antibodies and brain damage in autoimmune MRL mice.

Neuropsychiatric (NP) manifestations and brain pathology are poorly understood and potentially fatal concomitants of systemic lupus erythematosus (SLE). For many years, autoantibodies to brain tissue (i.e.

Disturbed distribution of proliferative brain cells during lupus-like disease.

Brain atrophy and neuronal degeneration of unknown etiology are frequent and severe concomitants of the systemic autoimmune disease lupus erythematosus (SLE). Using the murine MRL/lpr model, we examined populations of proliferative brain cells during the development of SLE-like disease and brain atrophy. The disease onset was associated with reduced expression of Ki67 and BrdU proliferation markers in the dorsal part of the rostral migratory stream, enhanced Fluoro Jade C staining in the subgranular zone of the dentate gyrus, and paradoxical increase in density of Ki67(+)/BrdU(-) cells in the paraventricular nucleus.

Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening.

Probiotics are live non-pathogenic commensal organisms that exert therapeutic effects in travellers' diarrhea, irritable bowel syndrome and inflammatory bowel disease. Little is known about mechanisms of action of commensal bacteria on intestinal motility and motility-induced pain. It has been proposed that probiotics affect intestinal nerve function, but direct evidence for this has thus far been lacking.