scholarly journals ROS-Induced mtDNA Release: The Emerging Messenger for Communication between Neurons and Innate Immune Cells during Neurodegenerative Disorder Progression

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1917
Author(s):  
Yuanxin Zhao ◽  
Buhan Liu ◽  
Long Xu ◽  
Sihang Yu ◽  
Jiaying Fu ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Cells ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Therapeutic Approaches ◽  
Inflammatory Microenvironment ◽  
Peripheral Immune Cells ◽  
The Relationship

One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis, is microglia-mediated and astrocyte-mediated neuroinflammation. Although inhibitions of both harmful proteins and aggregation are major treatments for neurodegenerative diseases, whether the phenomenon of non-normal protein or peptide aggregation is causally related to neuronal loss and synaptic damage is still controversial. Currently, excessive production of reactive oxygen species (ROS), which induces mitochondrial dysfunction in neurons that may play a key role in the regulation of immune cells, is proposed as a regulator in neurological disorders. In this review, we propose that mitochondrial DNA (mtDNA) release due to ROS may act on microglia and astrocytes adjacent to neurons to induce inflammation through activation of innate immune responses (such as cGAS/STING). Elucidating the relationship between mtDNA and the formation of a pro-inflammatory microenvironment could contribute to a better understanding of the mechanism of crosstalk between neuronal and peripheral immune cells and lead to the development of novel therapeutic approaches to neurodegenerative diseases.

scholarly journals Geometrical reorganization of Dectin-1 and TLR2 on single phagosomes alters their synergistic immune signaling

2019 ◽  
Vol 116 (50) ◽  
pp. 25106-25114 ◽  
Author(s):  
Wenqian Li ◽  
Jun Yan ◽  
Yan Yu
Keyword(s):  
Immune Responses ◽  
Immune Regulation ◽  
Spatial Organization ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Membrane Composition ◽  
Intracellular Compartments ◽  
Synergistic Regulation ◽  
The Relationship

Receptors of innate immune cells function synergistically to detect pathogens and elicit appropriate immune responses. Many receptor pairs also appear “colocalized” on the membranes of phagosomes, the intracellular compartments for pathogen ingestion. However, the nature of the seemingly receptor colocalization and the role it plays in immune regulation are unclear, due to the inaccessibility of intracellular phagocytic receptors. Here, we report a geometric manipulation technique to directly probe the role of phagocytic receptor “colocalization” in innate immune regulation. Using particles with spatially patterned ligands as phagocytic targets, we can decouple the receptor pair, Dectin-1 and Toll-like receptor (TLR)2, to opposite sides on a single phagosome or bring them into nanoscale proximity without changing the overall membrane composition. We show that Dectin-1 enhances immune responses triggered predominantly by TLR2 when their centroid-to-centroid proximity is <500 nm, but this signaling synergy diminishes upon receptor segregation beyond this threshold distance. Our results demonstrate that nanoscale proximity, not necessarily colocalization, between Dectin-1 and TLR2 is required for their synergistic regulation of macrophage immune responses. This study elucidates the relationship between the spatial organization of phagocytic receptors and innate immune responses. It showcases a technique that allows spatial manipulation of receptors and their signal cross-talk on phagosomes inside living cells.

scholarly journals Nanomaterial Exposure Induced Neutrophil Extracellular Traps: A New Target in Inflammation and Innate Immunity

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Hang Yang ◽  
Tony N. Marion ◽  
Yi Liu ◽  
Lingshu Zhang ◽  
Xue Cao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Immune Responses ◽  
Myeloid Cell ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Cell Type ◽  
Extracellular Traps ◽  
Pharmaceutical Industries ◽  
The Relationship

Nanotechnology has become a novel subject with impact in many research and technology areas. Nanoparticles (NPs), as a key component in nanotechnology, are widely used in many areas such as optical, magnetic, electrical, and mechanical engineering. The biomedical and pharmaceutical industries have embraced NPs as a viable drug delivery modality. As such, the potential for NP-induced cytotoxicity has emerged as a major concern for NP drug delivery systems. Thus, it is important to understand how NPs affect the innate immune system. As the most abundant myeloid cell type in innate immune responses, neutrophils are critical for concerns about potentially toxic side effects of NPs. When activated by innate immune stimuli, neutrophils may initiate NETosis to release neutrophil extracellular traps (NETs). Herein, we have reviewed the relationship between NPs and the induction of NETosis and release of NETs.

scholarly journals An Update on Innate Immune Responses during SARS-CoV-2 Infection

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2060
Author(s):  
Yu Zhang ◽  
Shuaiyin Chen ◽  
Yuefei Jin ◽  
Wangquan Ji ◽  
Weiguo Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Type I Interferons ◽  
Organ Injury ◽  
Type I ◽  
Innate Immune Responses ◽  
Innate Immune Signaling ◽  
Viral Proteases ◽  
Viral Components ◽  
The Relationship

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae family, which is responsible for the COVID-19 pandemic followed by unprecedented global societal and economic disruptive impact. The innate immune system is the body’s first line of defense against invading pathogens and is induced by a variety of cellular receptors that sense viral components. However, various strategies are exploited by SARS-CoV-2 to disrupt the antiviral innate immune responses. Innate immune dysfunction is characterized by the weak generation of type I interferons (IFNs) and the hypersecretion of pro-inflammatory cytokines, leading to mortality and organ injury in patients with COVID-19. This review summarizes the existing understanding of the mutual effects between SARS-CoV-2 and the type I IFN (IFN-α/β) responses, emphasizing the relationship between host innate immune signaling and viral proteases with an insight on tackling potential therapeutic targets.

scholarly journals Environment impacts innate immune ontogeny

2016 ◽  
Vol 23 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Mathieu Garand ◽  
Bing Cai ◽  
Tobias R Kollmann
Keyword(s):  
Immune Responses ◽  
Immune Modulation ◽  
Mononuclear Cells ◽  
Innate Immune ◽  
Racial Groups ◽  
Innate Immune Responses ◽  
Susceptibility To Infection ◽  
Cytokine Responses ◽  
Underlying Mechanisms ◽  
The Relationship

Susceptibility to infection and response to vaccination differ between populations and as a function of age. The underlying mechanisms for this age- and population-dependent variation are not known. Specifically, it is unclear if these variations are due to differences in genetically encoded host programs or driven by environmental influences or a combination of both. To address the relationship between gene and environment regarding immune ontogeny, we determined the innate cytokine responses following PRR stimulation of blood mononuclear cells at birth, 1, and 2 yr of age in infants from Caucasian vs . Asian parents and were raised in the same city. At birth, we found that innate cytokine responses were significantly elevated in Asian compared with Caucasian infants. However, these differences waned and responses became more similar over the course of 1–2 yr of living in a similar environment. Our observations that innate response differences present at birth subsequently equalized rather than diverged suggest a key role for environmental effects common to both racial groups in shaping the innate immune responses early in life. Delineating the underlying environmental factors that modulate innate immune responses early in life could provide avenues for targeted beneficial immune modulation.

scholarly journals Reprogramming Interferon Regulatory Factor Signaling in Cardiometabolic Diseases

Physiology ◽  
2017 ◽  
Vol 32 (3) ◽  
pp. 210-223 ◽  
Author(s):  
Yaxing Zhang ◽  
Hongliang Li
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Immune Cells ◽  
Interferon Regulatory Factor ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Regulatory Factor ◽  
Cardiometabolic Diseases ◽  
Evolutionarily Conserved

Interferon regulatory factors (IRFs) are evolutionarily conserved proteins expressed not only in immune cells but also in other tissues and organs outside the immune system. In this review, we discuss mechanisms responsible for IRF-mediated innate immune responses and the function and mechanism of IRFs in cardiometabolic diseases. We focus on the role of IRFs in innate immunity and cardiometabolic homeostasis, and highlight reprogrammed IRF signaling.

scholarly journals Managing Inflammation after Spinal Cord Injury through Manipulation of Macrophage Function

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yi Ren ◽  
Wise Young
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Immune Responses ◽  
Potential Effect ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Inflammatory Microenvironment ◽  
Persistent Inflammation ◽  
Cord Injury

Spinal cord injury (SCI) triggers inflammation with activation of innate immune responses that contribute to secondary injury including oligodendrocyte apoptosis, demyelination, axonal degeneration, and neuronal death. Macrophage activation, accumulation, and persistent inflammation occur in SCI. Macrophages are heterogeneous cells with extensive functional plasticity and have the capacity to switch phenotypes by factors present in the inflammatory microenvironment of the injured spinal cord. This review will discuss the role of different polarized macrophages and the potential effect of macrophage-based therapies for SCI.

Altered expression of talin 1 in peripheral immune cells points to a significant role of the innate immune system in spontaneous autoimmune uveitis

2012 ◽  
Vol 75 (14) ◽  
pp. 4536-4544 ◽  
Author(s):  
Roxane L. Degroote ◽  
Stefanie M. Hauck ◽  
Elisabeth Kremmer ◽  
Barbara Amann ◽  
Marius Ueffing ◽  
...  
Keyword(s):  
Immune System ◽  
Significant Role ◽  
Immune Cells ◽  
Innate Immune System ◽  
Innate Immune ◽  
Altered Expression ◽  
Autoimmune Uveitis ◽  
Peripheral Immune Cells

scholarly journals Relationship between Wine Consumption and Alzheimer's Disease

2019 ◽  
Author(s):  
Marcella Reale ◽  
Chiara D'Angelo ◽  
Erica Costantini ◽  
Srinivas Jagarlapoodi ◽  
Haroon Khan ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Alcohol Drinking ◽  
Senile Plaques ◽  
Neuronal Loss ◽  
Language Function ◽  
Wine Consumption ◽  
Reduce Risk ◽  
Main Factors ◽  
The Relationship

Background: Alzheimer&rsquo;s disease (AD), the most threatening neurodegenerative diseases, is characterized by the loss of memory and language function, an unbalanced perception of space and other cognitive and physical manifestations. Pathology of the AD is characterized by neuronal loss, and the extensive distribution of senile plaques and neurofibrillary tangles (NFTs). The role of environment and the diet in the AD is being studied actively, and nutrition is certainly one of the main factors playing a prominent role in the prevention of neurodegenerative diseases. In this context, the relationship between dementia and wine use/abuse has received increased research interest in recent times, with varying and often conflicting results. Scope and approach: This review aims to critically summarize the most recent studies conducted to clarify the relationship between wine drinking and AD, as well as whether effects are influenced by quantity and/or frequency of drinking. Key findings and Conclusion: Overall, based on the interpretation of various studies, it can be concluded that there is no indication that light to moderate alcohol drinking is detrimental to cognition and dementia, and it is not possible to define whether alcohol could be used as a means to reduce risk of developing AD.

scholarly journals Determinants of Innate Immunity in Visceral Leishmaniasis and Their Implication in Vaccine Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Greta Volpedo ◽  
Thalia Pacheco-Fernandez ◽  
Parna Bhattacharya ◽  
Timur Oljuskin ◽  
Ranadhir Dey ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Vaccine Development ◽  
Innate Immune ◽  
Epigenetic Reprogramming ◽  
Sand Fly ◽  
Innate Immune Cells ◽  
Innate Immune Responses ◽  
Inflammatory Monocytes

Leishmaniasis is endemic to the tropical and subtropical regions of the world and is transmitted by the bite of an infected sand fly. The multifaceted interactions between Leishmania, the host innate immune cells, and the adaptive immunity determine the severity of pathogenesis and disease development. Leishmania parasites establish a chronic infection by subversion and attenuation of the microbicidal functions of phagocytic innate immune cells such as neutrophils, macrophages and dendritic cells (DCs). Other innate cells such as inflammatory monocytes, mast cells and NK cells, also contribute to resistance and/or susceptibility to Leishmania infection. In addition to the cytokine/chemokine signals from the innate immune cells, recent studies identified the subtle shifts in the metabolic pathways of the innate cells that activate distinct immune signal cascades. The nexus between metabolic pathways, epigenetic reprogramming and the immune signaling cascades that drive the divergent innate immune responses, remains to be fully understood in Leishmania pathogenesis. Further, development of safe and efficacious vaccines against Leishmaniasis requires a broader understanding of the early interactions between the parasites and innate immune cells. In this review we focus on the current understanding of the specific role of innate immune cells, the metabolomic and epigenetic reprogramming and immune regulation that occurs during visceral leishmaniasis, and the strategies used by the parasite to evade and modulate host immunity. We highlight how such pathways could be exploited in the development of safe and efficacious Leishmania vaccines.

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