scholarly journals Cell Death in Coronavirus Infections: Uncovering Its Role during COVID-19

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1585
Author(s):  
Annamaria Paolini ◽  
Rebecca Borella ◽  
Sara De Biasi ◽  
Anita Neroni ◽  
Marco Mattioli ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Cells ◽  
Viral Infections ◽  
Virus Entry ◽  
Therapeutic Strategies ◽  
The Other ◽  
Cytokine Storm ◽  
Cytokines And Chemokines ◽  
Cell Death Mechanisms ◽  
The One

Cell death mechanisms are crucial to maintain an appropriate environment for the functionality of healthy cells. However, during viral infections, dysregulation of these processes can be present and can participate in the pathogenetic mechanisms of the disease. In this review, we describe some features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some immunopathogenic mechanisms characterizing the present coronavirus disease (COVID-19). Lymphopenia and monocytopenia are important contributors to COVID-19 immunopathogenesis. The fine mechanisms underlying these phenomena are still unknown, and several hypotheses have been raised, some of which assign a role to cell death as far as the reduction of specific types of immune cells is concerned. Thus, we discuss three major pathways such as apoptosis, necroptosis, and pyroptosis, and suggest that all of them likely occur simultaneously in COVID-19 patients. We describe that SARS-CoV-2 can have both a direct and an indirect role in inducing cell death. Indeed, on the one hand, cell death can be caused by the virus entry into cells, on the other, the excessive concentration of cytokines and chemokines, a process that is known as a COVID-19-related cytokine storm, exerts deleterious effects on circulating immune cells. However, the overall knowledge of these mechanisms is still scarce and further studies are needed to delineate new therapeutic strategies.

Exploration of beneficial and deleterious effects of inflammation in stroke: dynamics of inflammation cells

2009 ◽  
Vol 367 (1908) ◽  
pp. 4699-4716 ◽  
Author(s):  
Taïssia Lelekov-Boissard ◽  
Guillemette Chapuisat ◽  
Jean-Pierre Boissel ◽  
Emmanuel Grenier ◽  
Marie-Aimée Dronne
Keyword(s):  
Immune Cells ◽  
Blood Cells ◽  
Inflammatory Process ◽  
Living Cells ◽  
Therapeutic Strategies ◽  
Brain Parenchyma ◽  
Brain Cell ◽  
Cytokines And Chemokines ◽  
The Brain

The inflammatory process during stroke consists of activation of resident brain microglia and recruitment of leucocytes, namely neutrophils and monocytes/macrophages. During inflammation, microglial cells, neutrophils and macrophages secrete inflammatory cytokines and chemokines, and phagocytize dead cells. The recruitment of blood cells (neutrophils and macrophages) is mediated by the leucocyte–endothelium interactions and more specifically by cell adhesion molecules. A mathematical model is proposed to represent the dynamics of various brain cells and of immune cells (neutrophils and macrophages). This model is based on a set of six ordinary differential equations and explores the beneficial and deleterious effects of inflammation, respectively phagocytosis by immune cells and the release of pro-inflammatory mediators and nitric oxide (NO). The results of our simulations are qualitatively consistent with those observed in experiments in vivo and would suggest that the increase of phagocytosis could contribute to the increase of the percentage of living cells. The inhibition of the production of cytokines and NO and the blocking of neutrophil and macrophage infiltration into the brain parenchyma led also to the improvement of brain cell survival. This approach may help to explore the respective contributions of the beneficial and deleterious roles of the inflammatory process in stroke, and to study various therapeutic strategies in order to reduce stroke damage.

scholarly journals Moms, babies, and bugs in immune development

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2141
Author(s):  
Katie Alexander ◽  
Charles O. Elson
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Cells ◽  
Mucosal Immunity ◽  
The Other ◽  
Primary Role ◽  
Initial Development ◽  
Immune Development ◽  
The One

Bacteria and mammals have co-evolved with one another over millennia, and it has become impossible to interpret mucosal immunity without taking the microbiota into consideration. In fact, the primary role of the mucosal immune system is regulating homeostasis and the host relationship with the microbiota. Bacteria are no longer seen as simply invading pathogens, but rather a necessary component to one’s own immune response. On the one hand, the microbiota is a vital educator of immune cells and initiator of beneficial responses; but, on the other, dysbiosis of microbiota constituents are associated with inflammation and autoimmune disorders. In this review, we will consider recent advances in the understanding of how the microbiota influences host mucosal immunity, particularly the initial development of the immune response and its implications.

scholarly journals MECHANISMS OF CYTOKINE STORM DEVELOPMENT IN COVID-19 AND NEW POTENTIAL TARGETS OF PHARMACOTHERAPY

2021 ◽  
Vol 8 (6) ◽  
pp. 380-391
Author(s):  
V. I. Petrov ◽  
A. A. Amosov ◽  
A. S. Gerasimenko ◽  
O. V. Shatalova ◽  
A. V. Ponomareva ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Complement System ◽  
The Body ◽  
The Other ◽  
Cochrane Library ◽  
Cochrane Central Register ◽  
Cytokine Storm ◽  
Renin Angiotensin ◽  
Other Hand ◽  
The One

The development of a "cytokine storm", characteristic of severe COVID-19 forms, can be defined as a state of uncontrolled release of a large number of inflammatory mediators.The attachment of SARS-CoV-2 S-glycoprotein to angiotensin-converting enzyme 2 is considered a process that triggers complex molecular interactions that lead to hyperinflammation. In its turn, it is realized through several systems: renin-angiotensin-aldosterone, kallikrein-kinin and a complement system. Knowledge of these mechanisms suggests potential therapeutic interventions that can be targeted by existing therapeutic agents to counter the cytokine storm and treat the acute respiratory distress syndrome associated with COVID-19.The aim of the review article is to summarize the currently known data on the molecular processes underlying the uncontrolled "cytokine storm" in the patients with severe COVID-19, and possible options for their pharmacological correction.Materials and methods. The data base was represented by such systems as Medline, Cochrane Central Register of Controlled Trials, Scopus, Web of Science Core Collection, Cochrane Library, ClinicalTrials.gov, Elibrary, Google-Academy. A search was carried out for the following keywords and combinations: COVID-19, renin-angiotensin-aldosterone system, bradykinin, complement system, hyaluronic acid, pharmacotherapy.Results. The development of a "cytokine storm" in COVID-19 is mediated by pathogenetic changes in the body in response to the penetration of SARS-CoV-2 into the cell. In the RAAS, suppression of ACE2 leads to a decrease in its ability to degrade ATII, which, on the one hand, leads to a decrease in the amount of AT1-7, and, on the other hand, to the effect of ATII on AT1R with the subsequent development of vasoconstriction and lung damage. The disturbances in the kallikrein-kinin system are associated, on the one hand, with the increased expression of kallikrein and an increase in the formation of bradykinin and its metabolite des-Arg 9-bradykinin. On the other hand, the disturbances are associated with the suppression of the expression of the C1-esterase inhibitor which prevents the formation of kallikrein, and impaired inactivation of des-Arg 9-bradykinin under the action of ACE 2. The nucleocapsid protein SARS-CoV-2 triggers the activation of the complement system through the lectin pathway. It leads to the production of anaphylatoxins C3a and C5a, which stimulate the synthesis of pro-inflammatory cytokines. Proinflammatory cytokines are potent inducers of the HAS 2 gene in the endothelium, which encodes the membrane enzymes of hyaluronate synthase. The sweating of the fluid into the alveoli caused by the "bradykinin storm" in combination with the overproduction of hyaluronic acid, which accumulates water 1000 times its own mass, can lead to the formation of a dense jelly-like substance that prevents gas exchange.Conclusion. Promising areas of pharmacotherapy for "cytokine storm" are associated with its impact on the dysfunction of the listed above systems. However, the efficacy and safety of most drugs for the treatment of COVID-19, is to be studied through carefully designed clinical trials.

scholarly journals Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 91
Author(s):  
Alexandra Pum ◽  
Maria Ennemoser ◽  
Tiziana Adage ◽  
Andreas J. Kungl
Keyword(s):  
Host Response ◽  
Distress Syndrome ◽  
Therapeutic Strategies ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Severe Respiratory Distress ◽  
Cytokines And Chemokines ◽  
Severe Respiratory Distress Syndrome ◽  
Harmful Effects

The recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of coronavirus disease (COVID-19) and the associated ongoing pandemic, frequently leads to severe respiratory distress syndrome and pneumonia with fatal consequences. Although several factors of this infection and its consequences are not completely clear, the presence and involvement of specific chemokines is undoubtedly crucial for the development and progression of COVID-19. Cytokine storm and the often-resulting cytokine release syndrome (CRS) are pathophysiological hallmarks in COVID-19 infections related to its most severe and fatal cases. In this hyperinflammatory event, chemokines and other cytokines are highly upregulated and are therefore not fulfilling their beneficial function in the host response anymore but causing harmful effects. Here, we present the recent views on the involvement of chemokines and selected cytokines in COVID-19 and the therapeutics currently in clinical development targeting or interfering with them, discussing their potentials in the treatment of COVID-19 infections.

scholarly journals Role of the immune response in COVID-19

ANALES RANM ◽  
2020 ◽  
Vol 137 (137(02)) ◽  
pp. 113-116
Author(s):  
Emilio Gómez de la Concha
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Therapeutic Strategies ◽  
The Other ◽  
Current State ◽  
The Times ◽  
The One ◽  
Antiviral Control

Immune response plays a dual role in COVID-19 infection. On the one hand virus activates innate and adaptative immune responses that most of the times achieve antiviral control. On the other hand in a minority of patients uncontrolled inflammatory response may lead to harmful tissue damage. Here we summarize the current state of knowledge of the factors that contribute to disease severity and death and the rationale of the posible therapeutic strategies.

scholarly journals Triggers, Timescales, and Treatments for Cytokine-Mediated Tissue Damage

2020 ◽  
Author(s):  
David McBride ◽  
Matthew Kerr ◽  
Nicholas Dorn ◽  
Dora Ogbonna ◽  
Evan Santos ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Cytokine Production ◽  
Viral Infections ◽  
Immune Dysregulation ◽  
Therapeutic Strategies ◽  
Cytokine Storm ◽  
T Cell Therapy ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Successes And Challenges

Inflammation, an essential cytokine-mediated process for generating a neutralising immune response against pathogens, is generally protective. However, aberrant or excessive production of proinflammatory cytokines is associated with uncontrolled local and systemic inflammation, resulting in cell death and often irreversible tissue damage. Uncontrolled inflammation can manifest over timescales spanning hours to years and is primarily dependent on the triggering event. Rapid and potentially lethal increases in cytokine production, or ‘cytokine storm’, develops in hours to days, and is associated with cancer cell-based immunotherapies, such as chimeric antigen receptor T-cell therapy. On the other hand, some bacterial and viral infections with high microbial replication or highly potent antigens elicit immune responses that result in supraphysiological systemic cytokine concentrations, which manifest over days to weeks. Immune dysregulation in autoimmune diseases can lead to chronic cytokine-mediated tissue damage spanning months to years, which often occurs episodically. Upregulation of IL-1, IL-6, IFN-γ, TNF, and granulocyte macrophage colony-stimulating factor frequently coincides with cytokine storm, sepsis, and autoimmune disease. Inhibition of proinflammatory molecules via antagonist monoclonal antibodies has improved clinical outcomes, but the complexity of the underlying immune dysregulation results in high variability. Rather than a ‘one size fits all’ treatment approach, an identification of disease endotypes may permit the development of effective therapeutic strategies that address the contributors of disease progression. Here, the authors present a literature review of the cytokine-associated aetiology of acute and chronic cytokine-mediated tissue damage, describe successes and challenges in developing clinical treatments, and highlight advancements in preclinical therapeutic strategies for mitigating pathological cytokine production.

Cell Death Mechanisms and Potentially Cytotoxic Natural Immune Cells in Human Pregnancies Complicated by Preeclampsia

2013 ◽  
Vol 21 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Aliz Barakonyi ◽  
Eva Miko ◽  
Laszlo Szereday ◽  
Petra Dora Polgar ◽  
Timea Nemeth ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Cells ◽  
Cell Death Mechanisms

scholarly journals The role of autophagy and vesicular trafficking in melanoma development

2021 ◽  
Vol 67 (4) ◽  
pp. 480-484
Author(s):  
Iuliia Taskaeva ◽  
Anastasia Shatruk ◽  
Nataliya Bgatova
Keyword(s):  
Cell Death ◽  
Tumor Growth ◽  
Intracellular Transport ◽  
Literature Search ◽  
Vesicular Trafficking ◽  
The Other ◽  
Cancer Cell Death ◽  
Pubmed Database ◽  
The One

The role of autophagy and vesicular trafficking in carcinogenesis, including melanoma, is ambiguous: on the one hand, they contribute to the maintenance of intracellular homeostasis and the tumor progression, on the other hand, they can initiate cancer cell death. These processes have a significant impact on the metabolism of melanoma cells and could be associated with metastasis, tumor growth and progression. The review examines the mechanisms of autophagy and vesicular trafficking and presents the modern literature data demonstrating the role of the intracellular transport system in oncogenesis and melanoma development. A literature search was performed in the PubMed database.

Note on Selection of Coordinate Systems for Geodynamics

1975 ◽  
Vol 26 ◽  
pp. 395-407
Author(s):  
S. Henriksen
Keyword(s):  
Sea Level ◽  
The Other ◽  
Coordinate Systems ◽  
Mean Sea Level ◽  
The Earth ◽  
The One ◽  
Static Systems ◽  
Selection Of

The first question to be answered, in seeking coordinate systems for geodynamics, is: what is geodynamics? The answer is, of course, that geodynamics is that part of geophysics which is concerned with movements of the Earth, as opposed to geostatics which is the physics of the stationary Earth. But as far as we know, there is no stationary Earth – epur sic monere. So geodynamics is actually coextensive with geophysics, and coordinate systems suitable for the one should be suitable for the other. At the present time, there are not many coordinate systems, if any, that can be identified with a static Earth. Certainly the only coordinate of aeronomic (atmospheric) interest is the height, and this is usually either as geodynamic height or as pressure. In oceanology, the most important coordinate is depth, and this, like heights in the atmosphere, is expressed as metric depth from mean sea level, as geodynamic depth, or as pressure. Only for the earth do we find “static” systems in use, ana even here there is real question as to whether the systems are dynamic or static. So it would seem that our answer to the question, of what kind, of coordinate systems are we seeking, must be that we are looking for the same systems as are used in geophysics, and these systems are dynamic in nature already – that is, their definition involvestime.

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