scholarly journals Changes in Glycolytic Pathway in SARS-COV 2 Infection and Their Importance in Understanding the Severity of COVID-19

2021 ◽  
Vol 9 ◽  
Author(s):  
Adalberto Fernandes Santos ◽  
Pedro Póvoa ◽  
Paulo Paixão ◽  
António Mendonça ◽  
Luís Taborda-Barata
Keyword(s):  
Immune System ◽  
Glucose Metabolism ◽  
Epithelial Cells ◽  
Inflammatory Cytokines ◽  
Innate Immune System ◽  
Innate Immune ◽  
Glycolytic Pathway ◽  
Increase Glucose Uptake ◽  
High Doses ◽  
Pro Inflammatory Cytokines

COVID-19 is an infectious disease caused by Coronavirus 2 (SARS-CoV-2) that may lead to a severe acute respiratory syndrome. Such syndrome is thought to be related, at least in part, to a dysregulation of the immune system which involves three main components: hyperactivity of the innate immune system; decreased production of type 1 Interferons (IFN) by SARS-CoV-2-infected cells, namely respiratory epithelial cells and macrophages; and decreased numbers of both CD4+ and particularly CD8+ T cells. Herein, we describe how excessive activation of the innate immune system and the need for viral replication in several cells of the infected organism promote significant alterations in cells’ energy metabolism (glucose metabolism), which may underlie the poor prognosis of the disease in severe situations. When activated, cells of the innate immune system reprogram their metabolism, and increase glucose uptake to ensure secretion of pro-inflammatory cytokines. Changes in glucose metabolism are also observed in pulmonary epithelial cells, contributing to dysregulation of cytokine synthesis and inflammation of the pulmonary epithelium. Controlling hyperglycolysis in critically ill patients may help to reduce the exaggerated production of pro-inflammatory cytokines and optimise the actions of the adaptive immune system. In this review, we suggest that the administration of non-toxic concentrations of 2-deoxy-D-glucose, the use of GLUT 1 inhibitors, of antioxidants such as vitamin C in high doses, as well as the administration of N-acetylcysteine in high doses, may be useful complementary therapeutic strategies for these patients, as suggested by some clinical trials and/ or reports. Overall, understanding changes in the glycolytic pathway associated with COVID-19 infection can help to find new forms of treatment for this disease.

scholarly journals Vaccination against the Protozoan Parasite Histomonas meleagridis Primes the Activation of Toll-like Receptors in Turkeys and Chickens Determined by a Set of Newly Developed Multiplex RT-qPCRs

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 960
Author(s):  
Taniya Mitra ◽  
Beatrice Bramberger ◽  
Ivana Bilic ◽  
Michael Hess ◽  
Dieter Liebhart
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Host Species ◽  
Innate Immune System ◽  
Innate Immune ◽  
Post Inoculation ◽  
Avian Host ◽  
Toll Like Receptors ◽  
Immune System Activation ◽  
Pro Inflammatory Cytokines

Histomonosis in turkeys and chickens is caused by the extracellular parasite Histomonas meleagridis, but the outcome of the disease varies depending on the host species. So far, studies on the immune response against histomonosis focus mainly on different traits of the adaptive immune system. Activation of toll like receptors (TLR) leads to the interplay between cells of innate and adaptive immunity with consequences on B and T cell clonal expansion. Therefore, the present investigation focused on the interaction of virulent and/or attenuated histomonads with the innate immune system of turkeys and chickens at 4, 10, 21 days post inoculation. The expression of TLRs (TLR1A, 1B, 2A, 2B, 3, 4, 5, 6(Tu), 7, 13(Tu) and 21(Ch)) and pro-inflammatory cytokines (IL1β and IL6) were analysed in caecum and spleen samples by RT-qPCR. Most frequent significant changes in expression levels of TLRs were observed in the caecum following infection with virulent parasites, an effect noticed to a lower degree in tissue samples from birds vaccinated with attenuated parasites. TLR1B, 2B and 4 showed a continuous up-regulation in the caecum of both species during infection or vaccination, followed by challenge with virulent parasites. Vaccinated birds of both species showed a significant earlier change in TLR expression following challenge than birds kept non-vaccinated but challenged. Expression of TLRs and pro-inflammatory cytokines were associated with severe inflammation of diseased birds in the local organ caecum. In the spleen, changes in TLRs and pro-inflammatory cytokines were less prominent and mainly observed in turkey samples. In conclusion, a detailed comparison of TLRs and pro-inflammatory cytokines of the innate immune system following inoculation with attenuated and/or virulent H. meleagridis of two avian host species provides an insight into regulative mechanisms of TLRs in the development of protection and limitation of the disease.

scholarly journals Lithium: Immunomodulatory and Anti-Infectious Activities

2019 ◽  
Vol 4 (1) ◽  
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Human Body ◽  
Innate Immune System ◽  
Cell Types ◽  
Innate Immune ◽  
Signalling Pathways ◽  
Disease Models ◽  
Absolute Requirement ◽  
Different Cell Types

Lithium (Li), a well-known immunomodulatory agent, has been in use for the treatment of several infectious diseases. Li mainly acts through GSK3β inactivation and several other signalling pathways, which are directly involved in the activation of innate immune system. Li therapy has been shown to cause effective modulation of various inflammatory cytokines, and has also been shown to boost immunity in several disease models. Apart from treatment for mania, Li has also been proved to be effective against infections caused by viruses, bacteria, parasites, and certain life-style disorders. Its effects, ranging from common defensive capabilities to complex pathways for protection of human body, make Li extraordinary. Thus, Li is an absolute requirement that can be a solution for some of the immune related disorders. This review mainly focuses on pharmacology, immune reactions of different cell types, and anti-infectious activities of Li.

Basic Immunology

2019 ◽  
Author(s):  
Jonathan Lambourne ◽  
Ruaridh Buchanan
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Epithelial Cells ◽  
Immune Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Lymphoid Organs ◽  
Innate Immune ◽  
Adaptive Immune ◽  
Pathogen Entry

There are four major components of the immune system. These include: 1. mechanical barriers to pathogen entry. 2. the innate immune system. 3. the adaptive immune system. 4. the lymphoid organs. Mechanical barriers include skin and mucous membranes and tight junctions between epithelial cells prevent pathogen entry. Breaches can be iatrogenic, for example, IV lines, surgical wounds, and mucositis, and are a large source of healthcare- associated infections. The innate immune system provides the first internal line of defence, as well as initiating and shaping the adaptive immune response. The innate system comprises a range of responses: phagocytosis by neutrophils and macrophages (guided in part by the adaptive immune system), the complement cascade, and the release of antimicrobial peptides by epithelial cells (e.g. defensins, cathelicidin). The adaptive immune system includes both humoral (antibody- mediated) and cell-mediated responses. It is capable of greater diversity and specificity than the innate immune system, and can develop memory to pathogens and provide increased protection on re-exposure. Immune cells are divided into myeloid cells (neutrophils, eosinophils, basophils, mast cells, and monocytes/macrophages) and lymphoid cells (B, T, and NK cells). These all originate in the bone marrow from pluripotent haematopoietic stem cells. The lymphoid organs include the spleen, the lymph nodes, and mucosal-associated lymphoid tissues—which respond to antigens in the blood, tissues, and epithelial surfaces respectively. The three main ‘professional’ phagocytes are macrophages, dendritic cells, and neutrophils. They are similar with respect to how they recognize pathogens, but differ in their principal location and effector functions. Phagocytes express an array of Pattern Recognition Receptors (PRRs) e.g. Toll-like receptors and lectins (proteins that bind carbohydrates). PRRs recognize Pathogen- Associated Molecular Patterns (PAMPs)— elements which are conserved across species, such as cell-surface glycoproteins and nucleic acid sequences. Though limited in number, PRRs have evolved to recognize a huge array of pathogens. Binding of PRRs to PAMPs enhances phagocytosis. Macrophages are tissue-resident phagocytes, initiating and co-ordinating the local immune response. The cytokines and chemokines they produce cause vasodilation and alter the expression of endothelial cell adhesion factors, recruiting circulating immune cells.

scholarly journals Inhibition of Toll-like Receptor and Cytokine Signaling—A Unifying Theme in Ischemic Tolerance

2004 ◽  
Vol 24 (11) ◽  
pp. 1288-1304 ◽  
Author(s):  
Katalin Karikó ◽  
Drew Weissman ◽  
Frank A. Welsh
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Lipid Rafts ◽  
Inflammatory Cytokines ◽  
Innate Immune System ◽  
Endotoxin Tolerance ◽  
Ischemic Tolerance ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
The Brain

Cerebral ischemia triggers acute inflammation, which exacerbates primary brain damage. Activation of the innate immune system is an important component of this inflammatory response. Inflammation occurs through the action of proinflammatory cytokines, such as TNF, IL-1β and IL-6, that alter blood flow and increase vascular permeability, thus leading to secondary ischemia and accumulation of immune cells in the brain. Production of these cytokines is initiated by signaling through Toll-like receptors (TLRs) that recognize host-derived molecules released from injured tissues and cells. Recently, great strides have been made in understanding the regulation of the innate immune system, particularly the signaling mechanisms of TLRs. Negative feedback inhibitors of TLRs and inflammatory cytokines have now been identified and characterized. It is also evident that lipid rafts exist in membranes and play a role in receptor-mediated inflammatory signaling events. In the present review, using this newly available large body of knowledge, we take a fresh look at studies of ischemic tolerance. Based on this analysis, we recognize a striking similarity between ischemic tolerance and endotoxin tolerance, an immune suppressive state characterized by hyporesponsiveness to lipopolysaccharide (LPS). In view of this analogy, and considering recent discoveries related to molecular mechanisms of endotoxin tolerance, we postulate that inhibition of TLR and proinflammatory cytokine signaling contributes critically to ischemic tolerance in the brain and other organs. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Tolerance can be established with two temporal profiles: (i) a rapid form in which the trigger induces tolerance to ischemia within minutes and (ii) a delayed form in which development of protection takes several hours or days and requires de-novo protein synthesis. The rapid form of tolerance is achieved by direct interference with membrane fluidity, causing disruption of lipid rafts leading to inhibition of TLR/cytokine signaling pathways. In the delayed form of tolerance, the preconditioning stimulus first triggers the TLR/cytokine inflammatory pathways, leading not only to inflammation but also to simultaneous upregulation of feedback inhibitors of inflammation. These inhibitors, which include signaling inhibitors, decoy receptors, and anti-inflammatory cytokines, reduce the inflammatory response to a subsequent episode of ischemia. This novel interpretation of the molecular mechanism of ischemic tolerance highlights new avenues for future investigation into the prevention and treatment of stroke and related diseases.

Synergism between TLRs and NOD1/2 in Oral Epithelial Cells

2008 ◽  
Vol 87 (7) ◽  
pp. 682-686 ◽  
Author(s):  
A. Uehara ◽  
H. Takada
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Oral Bacteria ◽  
Innate Immune ◽  
Oral Epithelium ◽  
Innate Immune Responses ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
Pro Inflammatory Cytokines

Oral epithelium is the first barrier against oral bacteria in periodontal tissue. Oral epithelial cells constitutively express Toll-like receptors (TLRs) and NOD1/2, functional receptors which induce the production of antibacterial factors such as peptidoglycan recognition proteins (PGRPs) and β-defensin 2, but not pro-inflammatory cytokines such as interleukin (IL)-8. In this study, we hypothesized that innate immune responses in the oral epithelium are enhanced in inflamed tissue. We found that NOD1 and NOD2 agonists, in combination with TLR agonists, synergistically induced production of PGRPs and of β-defensin 2 in human oral epithelial cells via NF-κB. In contrast, co-stimulation with NOD1/2 and TLR ligands had no effect on the production of pro-inflammatory cytokines (IL-6, IL-8, and monocyte chemoattractant protein-1). These findings indicate that, in innate immune responses to invading microbes, a combination of signaling through TLRs and NODs leads to the synergistic activation of antibacterial responses in the oral epithelium.

scholarly journals Innate Immune Responses to Influenza Virus Infections in the Upper Respiratory Tract

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2090
Author(s):  
Edin J. Mifsud ◽  
Miku Kuba ◽  
Ian G. Barr
Keyword(s):  
Influenza Virus ◽  
Immune System ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Innate Immune System ◽  
Innate Immune ◽  
Upper Respiratory Tract ◽  
Adaptive Immune ◽  
Upper Respiratory

The innate immune system is the host’s first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must replicate in epithelial cells of the upper respiratory tract. However, there are several innate immune mechanisms in place to stop the virus from reaching epithelial cells. In addition to limiting viral replication and dissemination, the innate immune system also activates the adaptive immune system leading to viral clearance, enabling the respiratory system to return to normal homeostasis. However, an overzealous innate immune system or adaptive immune response can be associated with immunopathology and aid secondary bacterial infections of the lower respiratory tract leading to pneumonia. In this review, we discuss the mechanisms utilised by the innate immune system to limit influenza virus replication and the damage caused by influenza viruses on the respiratory tissues and how these very same protective immune responses can cause immunopathology.

scholarly journals Analysis of key molecules of the innate immune system in mammary epithelial cells isolated from marker-assisted and conventionally selected cattle

2009 ◽  
Vol 92 (9) ◽  
pp. 4621-4633 ◽  
Author(s):  
B. Griesbeck-Zilch ◽  
M. Osman ◽  
Ch. Kühn ◽  
M. Schwerin ◽  
R.H. Bruckmaier ◽  
...  
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Innate Immune System ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Innate Immune

Cytokine networking of innate immunity cells: a potential target of therapy

2014 ◽  
Vol 126 (9) ◽  
pp. 593-612 ◽  
Author(s):  
Ilja Striz ◽  
Eva Brabcova ◽  
Libor Kolesar ◽  
Alena Sekerkova
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Regulatory T Cells ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Extracellular Matrix Protein ◽  
Innate Immune Cells ◽  
Pro Inflammatory Cytokines

Innate immune cells, particularly macrophages and epithelial cells, play a key role in multiple layers of immune responses. Alarmins and pro-inflammatory cytokines from the IL (interleukin)-1 and TNF (tumour necrosis factor) families initiate the cascade of events by inducing chemokine release from bystander cells and by the up-regulation of adhesion molecules required for transendothelial trafficking of immune cells. Furthermore, innate cytokines produced by dendritic cells, macrophages, epithelial cells and innate lymphoid cells seem to play a critical role in polarization of helper T-cell cytokine profiles into specific subsets of Th1/Th2/Th17 effector cells or regulatory T-cells. Lastly, the innate immune system down-regulates effector mechanisms and restores homoeostasis in injured tissue via cytokines from the IL-10 and TGF (transforming growth factor) families mainly released from macrophages, preferentially the M2 subset, which have a capacity to induce regulatory T-cells, inhibit the production of pro-inflammatory cytokines and induce healing of the tissue by regulating extracellular matrix protein deposition and angiogenesis. Cytokines produced by innate immune cells represent an attractive target for therapeutic intervention, and multiple molecules are currently being tested clinically in patients with inflammatory bowel disease, rheumatoid arthritis, systemic diseases, autoinflammatory syndromes, fibrosing processes or malignancies. In addition to the already widely used blockers of TNFα and the tested inhibitors of IL-1 and IL-6, multiple therapeutic molecules are currently in clinical trials targeting TNF-related molecules [APRIL (a proliferation-inducing ligand) and BAFF (B-cell-activating factor belonging to the TNF family)], chemokine receptors, IL-17, TGFβ and other cytokines.

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