Modulation of Vagal Sensory Neurons via High Mobility Group Box-1 and Receptor for Advanced Glycation End Products: Implications for Respiratory Viral Infections

Mazzone, Stuart B.; Yang, Seung-Kwon; Keller, Jonathan M.; Simanauskaite, Juste; Arikkatt, Jaisy; Fogarty, Matthew J.; Moe, Aung Aung Kywe; Chen, Chen; Trewella, Matthew W.; Tian, Luyi; Ritchie, Matthew E.; Chua, Brendon Y.; Phipps, Simon; Short, Kirsty R.; McGovern, Alice E

doi:10.3389/fphys.2021.744812

Cited by 9 publications

(7 citation statements)

References 48 publications

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“…Animal studies also suggest that neural plasticity during pulmonary pathologies may relate to neuroinflammation within the vagus nerve or ganglia, characterized by increased inflammatory cell influx, upregulated inflammatory gene transcription and the release of inflammatory molecules from sensory neurons and resident or infiltrating immune cells 88 – 90 . The cause of this neuroinflammation is unclear, but likely relates to both peripheral vagal detection of tissue inflammation and adverse effects of inflammation-induced persistent firing of action potentials in sensory neurons 88 , 91 .…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Cough hypersensitivity and chronic cough

Chung

McGarvey

Song

et al. 2022

Nat Rev Dis Primers

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162

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Chronic cough is globally prevalent across all age groups. This disorder is challenging to treat because many pulmonary and extrapulmonary conditions can present with chronic cough, and cough can also be present without any identifiable underlying cause or be refractory to therapies that improve associated conditions. Most patients with chronic cough have cough hypersensitivity, which is characterized by increased neural responsivity to a range of stimuli that affect the airways and lungs, and other tissues innervated by common nerve supplies. Cough hypersensitivity presents as excessive coughing often in response to relatively innocuous stimuli, causing significant psychophysical morbidity and affecting patients’ quality of life. Understanding of the mechanisms that contribute to cough hypersensitivity and excessive coughing in different patient populations and across the lifespan is advancing and has contributed to the development of new therapies for chronic cough in adults. Owing to differences in the pathology, the organs involved and individual patient factors, treatment of chronic cough is progressing towards a personalized approach, and, in the future, novel ways to endotype patients with cough may prove valuable in management.

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Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Cough hypersensitivity and chronic cough

Chung

McGarvey

Song

et al. 2022

Nat Rev Dis Primers

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162

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“…We have previously shown that severe pulmonary IAV infections in mice are accompanied by a neuroinflammatory phenotype in the vagal sensory ganglia [19, 20]. To investigate whether peripheral sensory neuron activation in the lungs is involved in the development of vagal neuroinflammation, we compared the expression of inflammatory genes and inflammatory cell densities in the vagal sensory ganglia of IAV infected mice administered via inhalation from day 3 post IAV infection with either vehicle or QX-314 (Fig 2A).…”

Section: Resultsmentioning

confidence: 99%

“…We have previously shown that severe pulmonary IAV infections in mice are accompanied by a neuroinflammatory phenotype in the vagal sensory ganglia [19,20]…”

Section: Pharmacological Inhibition Of Pulmonary Sensory Neurons Impa...mentioning

confidence: 99%

Evidence for vagal sensory neural involvement in influenza pathogenesis and disease

Verzele,

Chua,

Short

et al. 2023

Preprint

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Influenza A virus (IAV) is a common respiratory pathogen and a global cause of significant and often severe morbidity. Although inflammatory immune responses to IAV infections are well described, little is known about how neuroimmune processes contribute to IAV pathogenesis. In the present study, we employed surgical, genetic, and pharmacological approaches to manipulate pulmonary vagal sensory neuron innervation and activity in the lungs to explore potential crosstalk between pulmonary sensory neurons and immune processes. Intranasal inoculation of mice with H1N1 strains of IAV resulted in stereotypical antiviral lung inflammation and tissue pathology, changes in breathing, loss of body weight and other clinical signs of severe IAV disease. Unilateral cervical vagotomy and genetic ablation of pulmonary vagal sensory neurons had a moderate effect on the pulmonary inflammation induced by IAV infection, but significantly worsened clinical disease presentation. Inhibition of pulmonary vagal sensory neuron activity via inhalation of the charged sodium channel blocker, QX-314, resulted in a moderate decrease in lung pathology, but again this was accompanied by a paradoxical worsening of clinical signs. Notably, vagal sensory ganglia neuroinflammation was induced by IAV infection and this was significantly potentiated by QX-314 administration. This vagal ganglia hyperinflammation was characterized by alterations in IAV-induced host defense gene expression, increased neuropeptide gene and protein expression, and an increase in the number of inflammatory cells present within the ganglia. These data suggest that pulmonary vagal sensory neurons play a role in the regulation of the inflammatory process during IAV infection and suggest that vagal neuroinflammation may be an important contributor to IAV pathogenesis and clinical presentation. Targeting these pathways could offer therapeutic opportunities to treat IAV-induced morbidity and mortality.

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“…One possibility is that the early processes leading to vagal sensory neuron damage establish a state of neuroinflammation within the vagal nerves and ganglia. This has been shown to occur following pathogen exposure in animal models of vagal hypersensitivity and is characterized by upregulated inflammatory cell influx into the nerve and ganglia, the activation of local glial cells, and the induction of proinflammatory genes [70][71][72]. Such a phenomenon might be expected to promote a state of sensory hypersensitivity in the period prior to sensory neuron destruction.…”

Section: Why Do Canvas Patients Have Chronic Cough?mentioning

confidence: 99%

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome: a neurogenic cough prototype

Guilleminault,

Mazzone,

Chazelas

et al. 2024

ERJ Open Res

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Chronic cough is a frequent disorder that is defined by a cough of more than 8 weeks duration. Despite extensive investigation, some patients exhibit no aetiology and others do not respond to specific treatments directed against apparent causes of cough. Such patients are identified as having unexplained or refractory chronic cough. Recently, a high proportion of patients with chronic cough in the context of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) was highlighted. CANVAS is a rare neurological disorder with a biallelic variation in the replication factor C subunit 1 (RFC1) gene corresponding mostly to an intronic AAGGG repeat expansion. Chronic cough in patients with CANVAS shares similar characteristics with cough hypersensitivity syndrome. The high prevalence of chronic cough in CANVAS gives the opportunity to better understand the neurogenic mechanism of chronic cough. In this review, we will describe the characteristics and mechanisms of CANVAS. We will also address the potential mechanisms responsible for chronic cough in CANVAS. Finally, we will address chronic cough management in the context of CANVAS.

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Modulation of Vagal Sensory Neurons via High Mobility Group Box-1 and Receptor for Advanced Glycation End Products: Implications for Respiratory Viral Infections

Cited by 9 publications

References 48 publications

Cough hypersensitivity and chronic cough

Cough hypersensitivity and chronic cough

Evidence for vagal sensory neural involvement in influenza pathogenesis and disease

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome: a neurogenic cough prototype

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