scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

scholarly journals Immune Response to the Pathogenesis of COVID-19 Infection: Possible Mechanism of Nutrition (Vitamins, Supplement) and Exercise

2021 ◽  
Author(s):  
Abdullahi Alausa ◽  
Rofiat Adeyemi ◽  
Barakat Olaleke ◽  
Aminat Ismail ◽  
Faith Sunday Oyelere
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Immune Dysfunction ◽  
Nutritional Intake ◽  
Moderate Exercise ◽  
The World ◽  
Positive Results

COVID-19 infection, a ravaging disease attributed to a SARS-CoV-like illness, has brought the world to its knee, causing a pandemic, with human-human transmission as a major source of the spread of this ailment. Alarmingly, this infection based on clinical manifestations is diagnosed as virus-induced pneumonia, with over 5 million cases with a mortality rate of about 7% (based on the recently published global report). However, most deaths have been associated with patients with underlying immune dysfunction or a compromised immunesystem. As no specific therapeutics and vaccines have been reported, the strengthening of the immune system through nutritional intake and exercise is essential. Also, previous studies have documented the immune-activating capabilities of Vitamin A and D, along with supplementary induction, yielding positive results in combating previous viral challenges. Typically, the gradual upsurge of T-lymphocytes and immune cell activities has been implemented by moderate exercise activities. This review examines the role of nutrition and exercise in immune system enhancement and proposes the possible mechanism of nutrition and exercise in combating COVID-19 infection.

scholarly journals Immunosenescence in Testicular Cancer Survivors: Potential Implications of Cancer Therapies and Psychological Distress

2021 ◽  
Vol 10 ◽  
Author(s):  
Silvia De Padova ◽  
Milena Urbini ◽  
Giuseppe Schepisi ◽  
Alessandra Virga ◽  
Elena Meggiolaro ◽  
...  
Keyword(s):  
Immune System ◽  
Testicular Cancer ◽  
Psychological Stress ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
T Cell Response ◽  
Premature Aging ◽  
High Dose ◽  
Hematopoietic Stem

Testicular cancer (TC) is the most frequent solid tumor diagnosed in young adult males. Although it is a curable tumor, it is frequently associated with considerable short-term and long-term morbidity. Both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system (immunosenescence) in TC survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases. Immunosenescence is a remodeling of immune cell populations with inversion of the CD4:CD8 ratio, accumulation of highly differentiated memory cells, shrinkage of telomeres, shift of T-cell response to Th2 type, and release of pro-inflammatory signals. TC survivors exposed to chemotherapy show features of immunological aging, including an increase in memory T-cells (CD4+ and CD8+) and high expression of the senescence biomarker p16INK4a in CD3+ lymphocytes. However, the plethora of factors involved in the premature aging of TC survivors make the situation more complex if we also take into account the psychological stress and hormonal changes experienced by patients, as well as the high-dose chemotherapy and hematopoietic stem cell transplantation that some individuals may be required to undergo. The relatively young age and the long life expectancy of TC patients bear witness to the importance of improving quality of life and of alleviating long-term side-effects of cancer treatments. Within this context, the present review takes an in-depth look at the molecular mechanisms of immunosenescence, describing experimental evidence of cancer survivor aging and highlighting the interconnected relationship between the many factors modulating the aging of the immune system of TC survivors.

scholarly journals Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence

2021 ◽  
Vol 22 (6) ◽  
pp. 3107
Author(s):  
Noemi Sola-Sevilla ◽  
Ana Ricobaraza ◽  
Ruben Hernandez-Alcoceba ◽  
Maria S. Aymerich ◽  
Rosa M. Tordera ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Potential Role ◽  
Adeno Associated Virus ◽  
Age Related ◽  
Age Dependent ◽  
Molecular Effects ◽  
Samp8 Mice ◽  
The Brain

Sirtuin 2 (SIRT2) has been associated to aging and age-related pathologies. Specifically, an age-dependent accumulation of isoform 3 of SIRT2 in the CNS has been demonstrated; however, no study has addressed the behavioral or molecular consequences that this could have on aging. In the present study, we have designed an adeno-associated virus vector (AAV-CAG-Sirt2.3-eGFP) for the overexpression of SIRT2.3 in the hippocampus of 2 month-old SAMR1 and SAMP8 mice. Our results show that the specific overexpression of this isoform does not induce significant behavioral or molecular effects at short or long term in the control strain. Only a tendency towards a worsening in the performance in acquisition phase of the Morris Water Maze was found in SAMP8 mice, together with a significant increase in the pro-inflammatory cytokine Il-1β. These results suggest that the age-related increase of SIRT2.3 found in the brain is not responsible for induction or prevention of senescence. Nevertheless, in combination with other risk factors, it could contribute to the progression of age-related processes. Understanding the specific role of SIRT2 on aging and the underlying molecular mechanisms is essential to design new and more successful therapies for the treatment of age-related diseases.

scholarly journals The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1280 ◽  
Author(s):  
Alessandro Maglione ◽  
Simona Rolla ◽  
Stefania Federica De Mercanti ◽  
Santina Cutrupi ◽  
Marinella Clerico
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Adaptive Immune System ◽  
Cell Types ◽  
Point Of View ◽  
Adaptive Immune ◽  
Future Path

Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease that leads to demyelination and neurodegeneration. The third trimester of pregnancy, which is characterized by high levels of estrogens, has been shown to be associated with reduced relapse rates compared with the rates before pregnancy. These effects could be related to the anti-inflammatory properties of estrogens, which orchestrate the reshuffling of the immune system toward immunotolerance to allow for fetal growth. The action of these hormones is mediated by the transcriptional regulation activity of estrogen receptors (ERs). Estrogen levels and ER expression define a specific balance of immune cell types. In this review, we explore the role of estradiol (E2) and ERs in the adaptive immune system, with a focus on estrogen-mediated cellular, molecular, and epigenetic mechanisms related to immune tolerance and neuroprotection in MS. The epigenome dynamics of immune systems are described as key molecular mechanisms that act on the regulation of immune cell identity. This is a completely unexplored field, suggesting a future path for more extensive research on estrogen-induced coregulatory complexes and molecular circuitry as targets for therapeutics in MS.

Abstract 562: Plgf is Crucial for the Hypertensive Response and T Cells Infiltration in Target Organs Induced by Angii

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Daniela Carnevale ◽  
Fabio Pallante ◽  
Valentina Fardella ◽  
Massimiliano De Lucia ◽  
Stefania Fardella ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Organ Damage ◽  
Central Moment ◽  
Immune System Activation ◽  
Target Organs ◽  
Main Components

Although several therapeutic strategies have been developed against the main components involved in blood pressure (BP) regulation, an optimum control in some hypertensive patients is still flawed, suggesting that mechanisms so far unidentified, sustain BP increase. Interestingly, an emerging area of investigation revealed that adaptive immunity is central in hypertension, since mice devoid of lymphocytes are protected from hypertension, and adoptive transfer of T cells, but not B cells, restores the typical hypertensive response. How hypertensive stimuli can afford this, still represents a fascinating enigma, challenging the search for molecular players, capable to bridge vascular responses to immunity and probably orchestrating the still unveiled role of immune system in hypertension. Among the manifold cytokines and inflammatory mediators, Placental Growth Factor (PlGF), belonging to a family of VEGF related angiogenic factors, caught our attention, given its role of “angiogenic cytokine” and its expression by cells of both the cardiovascular and the immune system. Moreover, it has also been recently shown that PlGF is secreted in vascular cells in response to AngII. Thus, we hypothesized that PlGF might recruit a selected type of immune cell, expressing its receptor VEGFR1, influencing the process of T cells activation during hypertensive challenges. We found that the typical hypertensive response induced by chronic AngII infusion, was completely prevented in mice with genetic deletion of PlGF, as well as the typical end organ damage induced by hypertension, i.e. cardiac hypertrophy, renal damage, microvascular rarefaction and immune cells infiltration in target organs. To determine whether the involvement of PlGF in immune system activation and T cells infiltration during AngII-induced hypertension had a causal role or was merely a consequence of the failure in BP raise, we analyzed both vessels and kidneys, early after AngII infusion, i.e. before BP increase. Strikingly, PlGF absence protected from early infiltration of both CD4+ and CD8+ T cells. Overall our data indicate that PlGF is a pivotal player in the molecular mechanisms activating immune system recruitment during an hypertensive challenge, a central moment in the increase in BP.

scholarly journals Selenium, Selenoproteins, and Immunity

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1203 ◽  
Author(s):  
Joseph Avery ◽  
Peter Hoffmann
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
High Throughput ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Biological Effects ◽  
Cell Functions ◽  
Experimental Systems ◽  
Physiological Processes

Selenium is an essential micronutrient that plays a crucial role in development and a wide variety of physiological processes including effect immune responses. The immune system relies on adequate dietary selenium intake and this nutrient exerts its biological effects mostly through its incorporation into selenoproteins. The selenoproteome contains 25 members in humans that exhibit a wide variety of functions. The development of high-throughput omic approaches and novel bioinformatics tools has led to new insights regarding the effects of selenium and selenoproteins in human immuno-biology. Equally important are the innovative experimental systems that have emerged to interrogate molecular mechanisms underlying those effects. This review presents a summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases.

scholarly journals Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
N. Muñoz-Durango ◽  
A. Vecchiola ◽  
L. M. Gonzalez-Gomez ◽  
F. Simon ◽  
C. A. Riedel ◽  
...  
Keyword(s):  
Immune System ◽  
Mineralocorticoid Receptor ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Scientific Work ◽  
Proinflammatory Mediators ◽  
Electrolyte Homeostasis

The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models.

scholarly journals The Neuroimmunology of Guillain-Barré Syndrome and the Potential Role of an Aging Immune System

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathleen M. Hagen ◽  
Shalina S. Ousman
Keyword(s):  
Immune System ◽  
Schwann Cells ◽  
Potential Role ◽  
Immune Cell ◽  
Guillain Barre Syndrome ◽  
Age Related ◽  
Guillain Barré Syndrome ◽  
Autoimmune Condition ◽  
Guillain Barré

Guillain-Barré syndrome (GBS) is a paralyzing autoimmune condition affecting the peripheral nervous system (PNS). Within GBS there are several variants affecting different aspects of the peripheral nerve. In general, there appears to be a role for T cells, macrophages, B cells, and complement in initiating and perpetuating attacks on gangliosides of Schwann cells and axons. Of note, GBS has an increased prevalence and severity with increasing age. In addition, there are alterations in immune cell functioning that may play a role in differences in GBS with age alongside general age-related declines in reparative processes (e.g., delayed de-differentiation of Schwann cells and decline in phagocytic ability of macrophages). The present review will explore the immune response in GBS as well as in animal models of several variants of the disorder. In addition, the potential involvement of an aging immune system in contributing to the increased prevalence and severity of GBS with age will be theorized.

Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease

2019 ◽  
Vol 26 (20) ◽  
pp. 3719-3753 ◽  
Author(s):  
Natasa Kustrimovic ◽  
Franca Marino ◽  
Marco Cosentino
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Neurodegenerative Disorder ◽  
Neurodegenerative Process ◽  
Progressive Degeneration ◽  
Cytokine Levels ◽  
Inflammatory Phenotype ◽  
Immune Challenges

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

mTORC and PKCε in Regulation of Alcohol Use Disorder

2020 ◽  
Vol 20 (17) ◽  
pp. 1696-1708 ◽  
Author(s):  
Athirah Hanim ◽  
Isa Naina Mohamed ◽  
Rashidi M. Pakri Mohamed ◽  
Srijit Das ◽  
Norefrina Shafinaz Md Nor ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Alcohol Intake ◽  
Potential Role ◽  
Synaptic Proteins ◽  
Cellular Mechanisms ◽  
Kinase C ◽  
Protein Kinase C Epsilon ◽  
Seeking Behavior

Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.

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