Interaction between microbiota and immunity in health and disease

Cell Research, Journal Year: 2020, Volume and Issue: 30(6), P. 492 - 506

Published: May 20, 2020

Abstract The interplay between the commensal microbiota and mammalian immune system development function includes multifold interactions in homeostasis disease. microbiome plays critical roles training of major components host’s innate adaptive system, while orchestrates maintenance key features host-microbe symbiosis. In a genetically susceptible host, imbalances microbiota-immunity under defined environmental contexts are believed to contribute pathogenesis multitude immune-mediated disorders. Here, we review microbiome-immunity crosstalk their health disease, providing examples molecular mechanisms orchestrating these intestine extra-intestinal organs. We highlight aspects current knowledge, challenges limitations achieving causal understanding host immune-microbiome interactions, as well impact on diseases, discuss how insights may translate towards future microbiome-targeted therapeutic interventions.

Language: Английский

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Overview of General and Discriminating Markers of Differential Microglia Phenotypes

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Aug. 6, 2020

Inflammatory processes and microglia activation accompanies most of the pathophysiological diseases in central nervous system. It is proven that glial pathology precedes even drives development multiple neurodegenerative conditions. A growing number studies point out importance brain as well physiological functioning. Those resident immune cells are divergent from peripherally infiltrated macrophages, but their precise situ discrimination surprisingly difficult. Microglia heterogeneity visible especially morphology, cell density particular structures, also expression cellular markers. This often determines role physiology or The species differences between rodent human markers add complexity to whole picture. Furthermore, due activation, shows a broad spectrum phenotypes ranging pro-inflammatory, potentially cytotoxic M1, anti-inflammatory, scavenging regenerative M2. distinction specific nowadays essential study microglial functions tissue state such quickly changing environment. Due overwhelming data on sets available for studies, choice appropriate scientific challenge. review gathers, classifies describes known recently discovered protein expressed by different phenotypes. Presented include qualitative semi-quantitative, general specific, surface intracellular proteins secreted molecules. Information provided here creates comprehensive practical guide trough current knowledge will allow choose proper, more detailed neuroinflammatory mechanisms various, physiological, pathological, Both, basic research clinical medicine, need clearly described validated molecular phenotype, diagnostics, treatment prevention engaging glia activation.

Language: Английский

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The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques

Cell Reports, Journal Year: 2019, Volume and Issue: 27(4), P. 1293 - 1306.e6

Published: April 1, 2019

Gene expression profiles of more than 10,000 individual microglial cells isolated from cortex and hippocampus male female App

Language: Английский

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Microglia Heterogeneity in the Single-Cell Era

Cell Reports, Journal Year: 2020, Volume and Issue: 30(5), P. 1271 - 1281

Published: Feb. 1, 2020

Microglia are resident immune cells in the central nervous system (CNS) that capable of carrying out prominent and various functions during development adulthood under both homeostatic disease conditions. Although microglia traditionally thought to be heterogeneous populations, which potentially allows them achieve a wide range responses environmental changes for maintenance CNS homeostasis, lack unbiased high-throughput methods assess heterogeneity has prevented study spatially temporally distributed subsets. The recent emergence novel single-cell techniques, such as cytometry by time-of-flight mass spectrometry (CyTOF) RNA sequencing, enabled scientists overcome limitations reveal surprising context-dependent microglia. In this review, we summarize current knowledge about spatial, temporal, functional diversity development, mice humans.

Language: Английский

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Microglia in Central Nervous System Inflammation and Multiple Sclerosis Pathology

Trends in Molecular Medicine, Journal Year: 2018, Volume and Issue: 25(2), P. 112 - 123

Published: Dec. 18, 2018

Language: Английский

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Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(4), P. 1912 - 1930

Published: Jan. 9, 2020

Type I interferon (IFN) is a key cytokine that curbs viral infection and cell malignancy. Previously, we demonstrated potent IFN immunogenicity of nucleic acid–containing (NA-containing) amyloid fibrils in the periphery. Here, investigated whether associated with β-amyloidosis inside brain contributes to neuropathology. An IFN-stimulated gene (ISG) signature was detected brains multiple murine Alzheimer disease (AD) models, phenomenon also observed WT mouse challenged generic NA-containing fibrils. In vitro, microglia innately responded AD activated ISG-expressing exclusively surrounded NA+ β plaques, which accumulated an age-dependent manner. Brain administration rIFN-β resulted microglial activation complement C3-dependent synapse elimination vivo. Conversely, selective receptor blockade effectively diminished ongoing microgliosis loss models. Moreover, enveloping neuritic plaques postmortem patients AD. Gene expression interrogation revealed pathway grossly upregulated clinical significantly correlated severity activation. Therefore, constitutes pivotal element within neuroinflammatory network critically neuropathogenic processes.

Language: Английский

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Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE

Nature Neuroscience, Journal Year: 2018, Volume and Issue: 22(2), P. 191 - 204

Published: Dec. 31, 2018

Language: Английский

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Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease Model

Neuron, Journal Year: 2019, Volume and Issue: 101(6), P. 1099 - 1108.e6

Published: Feb. 5, 2019

Language: Английский

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Inflammation and post‐traumatic stress disorder

Psychiatry and Clinical Neurosciences, Journal Year: 2019, Volume and Issue: 73(4), P. 143 - 153

Published: Jan. 17, 2019

While post-traumatic stress disorder (PTSD) is currently diagnosed based solely on classic psychological and behavioral symptoms, a growing body of evidence has highlighted link between this alterations in the immune inflammatory systems. Epidemiological studies have demonstrated that PTSD associated with significantly increased rates physical comorbidities which dysregulation involved, such as metabolic syndrome, atherosclerotic cardiovascular disease, autoimmune diseases. In line this, number blood biomarker reported compared to healthy controls, individuals exhibit elevated levels proinflammatory markers, interleukin-1β, interleukin-6, tumor necrosis factor-α, C-reactive protein. Moreover, various lines animal human research suggested inflammation not only but also can play an important role its pathogenesis pathophysiology. review, we first summarize suggestive PTSD. We then examine findings suggest possible mechanisms terms two different interrelated perspectives: putative causes activities potential consequences generates. Given there dearth treatment options for PTSD, possibilities new therapeutic approaches using pharmacological non-pharmacological treatments/interventions anti-inflammatory effects are discussed. Despite increasing attention given pathology remains much be elucidated, including more detailed inflammation, usefulness biomarkers diagnostic prognostic efficacy novel strategies targeting inflammation.

Language: Английский

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Immune cell regulation of glia during CNS injury and disease

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(3), P. 139 - 152

Published: Feb. 10, 2020

Language: Английский

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