Innate Immune Responses and Viral-Induced Neurologic Disease

Cheng, Yu-Ting; Skinner, Dominic D; Lane, Thomas E.

doi:10.3390/jcm8010003

Cited by 13 publications

(15 citation statements)

References 111 publications

(132 reference statements)

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“…Virus-specific T cells control viral replication through secretion of anti-viral cytokines and cytolytic activity. Sterile immunity is not achieved and virus persists within white matter tracts in surviving mice that subsequently develop an immune-mediated demyelinating disease (Bender and Weiss, 2010; Bergmann et al, 2006; Cheng et al, 2018; Lane and Hosking, 2010; Libbey et al, 2014). As is typical in this model, infected SPF mice reach peak clinical disease by day 10–11 post-infection (p.i.)…”

Section: Resultsmentioning

confidence: 99%

The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling

Brown

Soto

Yandamuri

et al. 2019

eLife

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Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.

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Section: Resultsmentioning

confidence: 99%

The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling

Brown

Soto

Yandamuri

et al. 2019

eLife

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“…Obesity and type 2 diabetes are linked to a chronic inflammatory response in multiple tissues, including adipose and brain tissue [63,64]. In the periphery, adipose tissue-derived pro-inflammatory and inflammatory mediators produced by activated resident brain inflammatory cells (astrocytes and microglia) enhance central inflammation in obesity [25,27].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer’s Like Pathology in Mice Brain

Hahm

Ullah

et al. 2020

Cells

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Oxidative stress and insulin resistance play major roles in numerous neurodegenerative diseases, including Alzheimer’s disease (AD). A high-fat diet induces obesity-associated oxidative stress, neuronal insulin resistance, microglial activation, and neuroinflammation, which are considered important risk factors for neurodegeneration. Obesity-related metabolic dysfunction is a risk factor for cognitive decline. The present study aimed to elucidate whether chronic consumption of a high-fat diet (HFD; 24 weeks) can induce insulin resistance, neuroinflammation, and amyloid beta (Aβ) deposition in mouse brains. Male C57BL/6N mice were used for a high-fat diet (HFD)-induced pre-clinical model of obesity. The protein expression levels were examined via Western blot, immunofluorescence, and the behavior analysis was performed using the Morris water maze test. To obtain metabolic parameters, insulin sensitivity and glucose tolerance tests were performed. We found that metabolic perturbations from the chronic consumption of HFD elevated neuronal oxidative stress and insulin resistance through adiponectin receptor (AdipoR1) suppression in HFD-fed mice. Similarly, our in vitro results also indicated that knockdown of AdipoR1 in the embryonic mouse hippocampal cell line mHippoE-14 leads to increased oxidative stress in neurons. In addition, HFD markedly increased neuroinflammatory markers’ glial activation in the cortex and hippocampus regions of HFD mouse brains. More importantly, we observed that AdipoR1 suppression increased the amyloidogenic pathway both in vivo and in vitro. Furthermore, deregulated synaptic proteins and behavioral deficits were observed in the HFD mouse brains. Taken together, our findings suggest that excessive consumption of an HFD has a profound impact on brain function, which involves the acceleration of cognitive impairment due to increased obesity-associated oxidative stress, insulin resistance, and neuroinflammation, which ultimately may cause early onset of Alzheimer’s pathology via the suppression of AdipoR1 signaling in the brain.

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“…et al, 2020 ). Neutrophil reactive oxygen species (ROS) and NETs participate in demyelination of the central neural system in mice with neurological diseases and coronavirus infection ( Cheng et al, 2019 ). Therefore, treatments targeting excessive neutrophil activation may improve pathological neutrophilic inflammation during COVID-19 infection complicated by ARDS and nerve invasion.…”

Section: Contribution Of Neutrophils To Covid-19 Associated Ardsmentioning

confidence: 99%

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

et al. 2020

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This review describes targeting neutrophils as a potential therapeutic strategy for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19), a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutrophil counts are significantly elevated in patients with COVID-19 and significantly correlated with disease severity. The neutrophil-to-lymphocyte ratio can serve as a clinical marker for predicting fatal complications related to ARDS in patients with COVID-19. Neutrophil-associated inflammation plays a critical pathogenic role in ARDS. The effector functions of neutrophils, acting as respiratory burst oxidants, granule proteases, and neutrophil extracellular traps, are linked to the pathogenesis of ARDS. Hence, neutrophils can not only be used as pathogenic markers but also as candidate drug targets for COVID-19 associated ARDS.

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Innate Immune Responses and Viral-Induced Neurologic Disease

Cited by 13 publications

References 111 publications

The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling

The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer’s Like Pathology in Mice Brain

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

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