Immunoregulatory effect of mast cells influenced by microbes in neurodegenerative diseases

Girolamo, Francesco; Coppola, Cristiana; Ribatti, Doménico

doi:10.1016/j.bbi.2017.06.017

Cited by 49 publications

(31 citation statements)

References 472 publications

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“…Mast cells mediate BBB permeability and recruitment of immune cells into the brain, sustaining CNS inflammation in a potentially detrimental manner . Recent studies show that mast cells interact with the gut microbiota and gut permeability, and may therefore influence many diseases in which the gut microbiota is of importance, including MS, AD, ALS, PD and epilepsy …”

Section: Innate Immunitymentioning

confidence: 99%

Inflammation in CNS neurodegenerative diseases

et al. 2018

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Neurodegenerative diseases, the leading cause of morbidity and disability, are gaining increased attention as they impose a considerable socioeconomic impact, due in part to the ageing community. Neuronal damage is a pathological hallmark of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, Huntington's disease, spinocerebellar ataxia and multiple sclerosis, although such damage is also observed following neurotropic viral infections, stroke, genetic white matter diseases and paraneoplastic disorders. Despite the different aetiologies, for example, infections, genetic mutations, trauma and protein aggregations, neuronal damage is frequently associated with chronic activation of an innate immune response in the CNS. The growing awareness that the immune system is inextricably involved in shaping the brain during development as well as mediating damage, but also regeneration and repair, has stimulated therapeutic approaches to modulate the immune system in neurodegenerative diseases. Here, we review the current understanding of how astrocytes and microglia, as well as neurons and oligodendrocytes, shape the neuroimmune response during development, and how aberrant responses that arise due to genetic or environmental triggers may predispose the CNS to neurodegenerative diseases. We discuss the known interactions between the peripheral immune system and the brain, and review the current concepts on how immune cells enter and leave the CNS. A better understanding of neuroimmune interactions during development and disease will be key to further manipulating these responses and the development of effective therapies to improve quality of life, and reduce the impact of neuroinflammatory and degenerative diseases.

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Section: Innate Immunitymentioning

confidence: 99%

Inflammation in CNS neurodegenerative diseases

et al. 2018

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“…Mediators derived from mast cells [40,60,83] could activate microglia [38,95], causing localized inflammation [47,[96][97][98] and leading to symptoms of ASD [39]. Triggers of mast cells can reach the hypothalamus from the nasal cavity through the cribriform plexus [99], or through the brain lymphatics [100].…”

Section: Mast Cells and Neuroinflammationmentioning

confidence: 99%

“…As a result, mast cells are critical for different pathophysiological processes [77], not only allergic reactions [78], but also innate and acquired immunity [79,80], antigen presentation [81,82] and inflammation [60,83].In addition to immunoglobulin E (IgE) and specific allergens, mast cells are stimulated by bacteria, drugs, foods, fungi, heavy metals, organophosphates and viruses, as well as certain neuropeptides including corticotropin-releasing hormone (CRH) [84], neurotensin (NT) [85,86] and substance P (SP) [87,88]. Both NT [89,90] and SP [91][92][93][94] are known to participate in inflammatory processes.Mediators derived from mast cells [40,60,83] could activate microglia [38,95], causing localized inflammation [47,[96][97][98] and leading to symptoms of ASD [39]. Triggers of mast cells can reach the hypothalamus from the nasal cavity through the cribriform plexus [99], or through the brain lymphatics [100].…”

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confidence: 99%

Mast Cells, Stress, Fear and Autism Spectrum Disorder

Theoharides

Kavalioti

Tsilioni

2019

IJMS

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Autism Spectrum Disorder (ASD) is a developmental condition characterized by impaired communication and obsessive behavior that affects 1 in 59 children. ASD is expected to affect 1 in about 40 children by 2020, but there is still no distinct pathogenesis or effective treatments. Prenatal stress has been associated with higher risk of developing ASD in the offspring. Moreover, children with ASD cannot handle anxiety and respond disproportionately even to otherwise benign triggers. Stress and environmental stimuli trigger the unique immune cells, mast cells, which could then trigger microglia leading to abnormal synaptic pruning and dysfunctional neuronal connectivity. This process could alter the “fear threshold” in the amygdala and lead to an exaggerated “fight-or-flight” reaction. The combination of corticotropin-releasing hormone (CRH), secreted under stress, together with environmental stimuli could be major contributors to the pathogenesis of ASD. Recognizing these associations and preventing stimulation of mast cells and/or microglia could greatly benefit ASD patients.

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“…MCs are key players in many physiological and pathological processes, including allergy, asthma, autoimmunity, infectious disease, cancer and even many central nervous system disorders such as autism, anxiety and multiple sclerosis (Galli et al, 2005;Girolamo, Coppola, & Ribatti, 2017;Metcalfe, Baram, & Mekori, 1997;Silver & Curley, 2013;Williams & Galli, 2000). Therefore, inhibition of MC function has many potential consequences on human health.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial agent triclosan suppresses mast cell signaling via phospholipase D inhibition

Shim

Caron

Weatherly

et al. 2019

J of Applied Toxicology

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Humans are exposed to the antimicrobial agent triclosan (TCS) through use of TCS‐containing products. Exposed tissues contain mast cells, which are involved in numerous biological functions and diseases by secreting various chemical mediators through a process termed degranulation. We previously demonstrated that TCS inhibits both Ca2+ influx into antigen‐stimulated mast cells and subsequent degranulation. To determine the mechanism linking the TCS cytosolic Ca2+ depression to inhibited degranulation, we investigated the effects of TCS on crucial signaling enzymes activated downstream of the Ca2+ rise: protein kinase C (PKC; activated by Ca2+ and reactive oxygen species [ROS]) and phospholipase D (PLD). We found that TCS strongly inhibits PLD activity within 15 minutes post‐antigen, a key mechanism of TCS mast cell inhibition. In addition, experiments using fluorescent constructs and confocal microscopy indicate that TCS delays antigen‐induced translocations of PKCβII, PKCδ and PKC substrate myristoylated alanine‐rich C‐kinase. Surprisingly, TCS does not inhibit PKC activity or overall ability to translocate, and TCS actually increases PKC activity by 45 minutes post‐antigen; these results are explained by the timing of both TCS inhibition of cytosolic Ca2+ (~15+ minutes post‐antigen) and TCS stimulation of ROS (~45 minutes post‐antigen). These findings demonstrate that it is incorrect to assume that all Ca2+‐dependent processes will be synchronously inhibited when cytosolic Ca2+ is inhibited by a toxicant or drug. The results offer molecular predictions of the effects of TCS on other mammalian cell types, which share these crucial signal transduction elements and provide biochemical information that may underlie recent epidemiological findings implicating TCS in human health problems.

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Immunoregulatory effect of mast cells influenced by microbes in neurodegenerative diseases

Cited by 49 publications

References 472 publications

Inflammation in CNS neurodegenerative diseases

Inflammation in CNS neurodegenerative diseases

Mast Cells, Stress, Fear and Autism Spectrum Disorder

Antimicrobial agent triclosan suppresses mast cell signaling via phospholipase D inhibition

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