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1.
Int J Biol Sci ; 18(1): 386-408, 2022.
Article in English | MEDLINE | ID: covidwho-1607858

ABSTRACT

Responding to the coronavirus disease 2019 (COVID-19) pandemic has been an unexpected and unprecedented global challenge for humanity in this century. During this crisis, specialists from the laboratories and frontline clinical personnel have made great efforts to prevent and treat COVID-19 by revealing the molecular biological characteristics and epidemic characteristics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, SARS-CoV-2 has severe consequences for public health, including human respiratory system, immune system, blood circulation system, nervous system, motor system, urinary system, reproductive system and digestive system. In the review, we summarize the physiological and pathological damage of SARS-CoV-2 to these systems and its molecular mechanisms followed by clinical manifestation. Concurrently, the prevention and treatment strategies of COVID-19 will be discussed in preclinical and clinical studies. With constantly unfolding and expanding scientific understanding about COVID-19, the updated information can help applied researchers understand the disease to build potential antiviral drugs or vaccines, and formulate creative therapeutic ideas for combating COVID-19 at speed.


Subject(s)
COVID-19/pathology , COVID-19/therapy , Immunotherapy/methods , SARS-CoV-2 , Animals , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19 Vaccines , Cytokines/metabolism , Female , Humans , Immune System , Immunity, Innate , Immunologic Memory , Male , Mice
2.
Int J Environ Res Public Health ; 19(1)2021 Dec 23.
Article in English | MEDLINE | ID: covidwho-1580844

ABSTRACT

The perennial emergence of SARS-CoV-2 and its new variants causing upper respiratory complexities since December 2019 has aggravated the pandemic situation around the world. SARS-CoV-2 encodes several proteins among which ORF8 is a novel factor that is unique to SARS-CoV-2 only and is reported to help the virus in disease severity and immune evasion. ORF8-IRF3 complex induces endoplasmic reticulum stress, thus helps in the evasion of immune response. Consequently, targeting the ORF8-IRF3 complex is considered as a prime target for the discovery of novel drugs against SARS-CoV-2. In this regard, computational methods are of great interest to fast track the identification and development of novel drugs. Virtual screening of South African Natural Compounds Database (SANCDB), followed by docking and molecular dynamics (MD) simulation analysis, were performed to determine novel natural compounds. Computational molecular search and rescoring of the SANCDB database followed by induced-fit docking (IFD) protocol identified Quercetin 3-O-(6″-galloyl)-beta-D-galactopyranoside (SANC00850), Tribuloside (SANC01050), and Rutin (SANC00867) are the best scoring compounds. Structural-dynamic properties assessment revealed that these three compounds have stable dynamics, compactness, and a higher number of hydrogen bonds. For validation, we used MM/GBSA, in silico bioactivity estimation and dissociation constant (KD) approaches, which revealed that these compounds are the more potent inhibitors of the ORF8-IRF3 complex and would rescue the host immune system potentially. These compounds need further in vitro and in vivo validations to be used as therapeutics against SARS-CoV-2 to rescue the host immune system during COVID-19 infection.


Subject(s)
Biological Products , COVID-19 , Antigen-Antibody Complex , Humans , Immune Evasion , Immune System , Interferon Regulatory Factor-3 , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2
3.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Article in English | MEDLINE | ID: covidwho-1573990

ABSTRACT

The positive impact of meditation on human well-being is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole-blood gene expression profiling combined with multilevel bioinformatic analyses to characterize the coexpression, transcriptional, and protein-protein interaction networks to identify a meditation-specific core network after an advanced 8-d Inner Engineering retreat program. We found the response to oxidative stress, detoxification, and cell cycle regulation pathways were down-regulated after meditation. Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon signaling, were up-regulated, with no significant expression changes in the inflammatory genes. This robust meditation-specific immune response network is significantly dysregulated in multiple sclerosis and severe COVID-19 patients. The work provides a foundation for understanding the effect of meditation and suggests that meditation as a behavioral intervention can voluntarily and nonpharmacologically improve the immune response for treating various conditions associated with excessive or persistent inflammation with a dampened immune system profile.


Subject(s)
Immune System/metabolism , Meditation , Transcriptome , Adult , COVID-19/immunology , COVID-19/metabolism , Diet, Vegan , Female , Genome, Human , Humans , Male , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Protein Interaction Maps
4.
Clin Transl Med ; 11(12): e680, 2021 12.
Article in English | MEDLINE | ID: covidwho-1568017

ABSTRACT

Omicron variants are part of the "Coronavirus disease 2019 [COVID-19] Variants of Concerns" and has the potential to spread around the world rapidly and can harm human life. We can anticipate that the endemic state of COVID-19 will be characterized by the development of new strains with surges that will predominate in unvaccinated and immunodeficient populations. Thus, there will be an important role in promoting vaccinations, boosters and accessible testing to prevent disease transmission and to rapidly detect surges. There is an urgent need to explore the virology and biology of Omicron variants, define clinical phenomes and therapies, monitor dynamics of genetic changes, and translate the knowledge of COVID-19 into new variants. Clinical and translational medicine will be impactful in addressing these challenges by providing new insights for understanding and predicting new variants-associated transmissibility, disease severity, immune escape, diagnostic or therapeutic failure.


Subject(s)
COVID-19/prevention & control , COVID-19/virology , SARS-CoV-2/genetics , /methods , COVID-19 Vaccines , Humans , Immune System , Mutation , South Africa , Vaccination
5.
Clin Transl Med ; 11(12): e668, 2021 12.
Article in English | MEDLINE | ID: covidwho-1568016

ABSTRACT

The level of postvaccine protection depends on two factors: antibodies and T-cell responses. While the first one is relatively easily measured, the measuring of the second one is a difficult problem. The recent studies indicate that the first one may be a good proxy for the protection, at least for SARS-CoV-2. The massive data currently gathered by both researcher and citizen scientists may be pivotal in confirming this observation, and the collective body of evidence is growing daily. This leads to an acceptance of IgG antibody levels as an accessible biomarker of individual's protection. With enormous and immediate need for assessing patient condition at the point of care, quantitative antibody analysis remains the most effective and efficient way to assess the protection against the disease. Let us not discount importance of reference points in the turmoil of current pandemics.


Subject(s)
Antibodies, Viral/chemistry , Antibodies/chemistry , Biomarkers/metabolism , COVID-19/blood , COVID-19/immunology , Antibody Specificity , Humans , Immune System , Immunity , Immunoglobulin G/metabolism , Intensive Care Units , Pandemics , Point-of-Care Systems , SARS-CoV-2 , Serologic Tests/methods , Serologic Tests/standards , Vaccines
7.
Life Sci Alliance ; 5(3)2022 03.
Article in English | MEDLINE | ID: covidwho-1552086

ABSTRACT

Murine neural stem cells (NSCs) were recently shown to release piRNA-containing exosomes/microvesicles (Ex/Mv) for exerting antiviral immunity, but it remains unknown if these Ex/Mv could target SARS-CoV-2 and whether the PIWI-piRNA system is important for these antiviral actions. Here, using in vitro infection models, we show that hypothalamic NSCs (htNSCs) Ex/Mv provided an innate immunity protection against SARS-CoV-2. Importantly, enhanced antiviral actions were achieved by using induced Ex/Mv that were derived from induced htNSCs through twice being exposed to several RNA fragments of SARS-CoV-2 genome, a process that was designed not to involve protein translation of these RNA fragments. The increased antiviral effects of these induced Ex/Mv were associated with increased expression of piRNA species some of which could predictably target SARS-CoV-2 genome. Knockout of piRNA-interacting protein PIWIL2 in htNSCs led to reductions in both innate and induced antiviral effects of Ex/Mv in targeting SARS-CoV-2. Taken together, this study demonstrates a case suggesting Ex/Mv from certain cell types have innate and adaptive immunity against SARS-CoV-2, and the PIWI-piRNA system is important for these antiviral actions.


Subject(s)
Argonaute Proteins/metabolism , COVID-19/immunology , COVID-19/metabolism , Cell-Derived Microparticles/metabolism , Exosomes , RNA, Small Interfering/metabolism , RNA/metabolism , SARS-CoV-2 , A549 Cells , Angiotensin-Converting Enzyme 2/metabolism , Animals , Genome, Viral , Humans , Hypothalamus/metabolism , Immune System , Immunity, Innate , In Vitro Techniques , Mice
8.
J Med Virol ; 93(12): 6671-6685, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544318

ABSTRACT

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of syndromes involving multiple organ systems and is primarily mediated by viral spike (S) glycoprotein through the receptor-binding domain (RBD) and numerous cellular proteins including ACE2, transmembrane serine protease 2 (TMPRSS2), kidney injury molecule-1 (Kim-1), and neuropilin-1 (NRP-1). In this study, we examined the entry tropism of SARS-CoV-2 and SARS-CoV using S protein-based pseudoviruses to infect 22 cell lines and 3 types of primary cells isolated from respiratory, urinary, digestive, reproductive, and immune systems. At least one cell line or type of primary cell from each organ system was infected by both pseudoviruses. Infection by pseudoviruses is effectively blocked by S1, RBD, and ACE2 recombinant proteins, and more weakly by Kim-1 and NRP-1 recombinant proteins. Furthermore, cells with robust SARS-CoV-2 pseudovirus infection had strong expression of either ACE2 or Kim-1 and NRP-1 proteins. ACE2 glycosylation appeared to be critical for the infections of both viruses as there was a positive correlation between infectivity of either SARS-CoV-2 or SARS-CoV pseudovirus with the level of glycosylated ACE2 (gly-ACE2). These results reveal that SARS-CoV-2 cell entry could be mediated by either an ACE2-dependent or -independent mechanism, thus providing a likely molecular basis for its broad tropism for a wide variety of cell types.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Gastrointestinal Tract/virology , Genitalia/virology , Hepatitis A Virus Cellular Receptor 1/metabolism , Immune System/virology , Neuropilin-1/metabolism , Respiratory System/virology , SARS-CoV-2/physiology , Serine Endopeptidases/metabolism , Virus Internalization , Blotting, Western , COVID-19/metabolism , COVID-19/virology , Cell Line , Cells, Cultured , Fluorescent Antibody Technique , Gastrointestinal Tract/cytology , Genitalia/cytology , Humans , Immune System/cytology , Respiratory System/cytology
9.
Cell Rep ; 37(3): 109838, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1517083

ABSTRACT

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow rapid characterization, they do not fully recapitulate the dynamic interaction of virions and neutralizing antibodies in the airway. Here, we demonstrate that the N501Y variant permits respiratory infection in unmodified mice. We utilize N501Y to survey in vivo pseudovirus infection dynamics and susceptibility to reinfection with the L452R (Los Angeles), K417N + E484K (South Africa), and L452R + K417N + E484Q (India) variants. Human coronavirus disease 2019 (COVID-19)+ or vaccinated antibody isotypes, titers, variant receptor binding domain (RBD) binding, and neutralization potential are studied, revealing numerous significant correlations. Immune escape of the K417N + E484K variant is observed because infection can be appreciated in the nasopharynx, but not lungs, of mice transferred with low-antibody-tier plasma. Conversely, near-complete protection is observed in animals receiving high-antibody-tier plasma, a phenomenon that can only be appreciated in vivo.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Cell Line , Cricetinae , Genetic Variation , HEK293 Cells , Humans , Immune System , Immunization, Passive/methods , In Vitro Techniques , Mice , Mutation , Nasopharynx/virology , Protein Binding , Recombinant Proteins/metabolism , Spike Glycoprotein, Coronavirus/genetics
10.
Methods Mol Biol ; 2386: 43-60, 2022.
Article in English | MEDLINE | ID: covidwho-1513947

ABSTRACT

A comprehensive study of the cellular components of the immune system demands both deep and broad immunophenotyping of numerous cell subsets in an effective and practical way. Novel full-spectrum technology reveals the complete emission spectrum of each dye maximizing the amount of information that can be obtained on a single sample regarding conventional flow cytometry and provide an expanded knowledge of biological processes. In this chapter, we describe a 37-color protocol that allows to identify more than 45 different cell populations on whole blood samples of SARS-CoV-2-infected patients.


Subject(s)
COVID-19 , Flow Cytometry , Immunophenotyping/methods , COVID-19/blood , Color , Humans , Immune System
11.
Immunology ; 164(4): 722-736, 2021 12.
Article in English | MEDLINE | ID: covidwho-1494730

ABSTRACT

Bruton's tyrosine kinase (BTK) is a TEC kinase with a multifaceted role in B-cell biology and function, highlighted by its position as a critical component of the B-cell receptor signalling pathway. Due to its role as a therapeutic target in several haematological malignancies including chronic lymphocytic leukaemia, BTK has been gaining tremendous momentum in recent years. Within the immune system, BTK plays a part in numerous pathways and cells beyond B cells (i.e. T cells, macrophages). Not surprisingly, BTK has been elucidated to be a driving factor not only in lymphoproliferative disorders but also in autoimmune diseases and response to infection. To extort this role, BTK inhibitors such as ibrutinib have been developed to target BTK in other diseases. However, due to rising levels of resistance, the urgency to develop new inhibitors with alternative modes of targeting BTK is high. To meet this demand, an expanding list of BTK inhibitors is currently being trialled. In this review, we synopsize recent discoveries regarding BTK and its role within different immune cells and pathways. Additionally, we discuss the broad significance and relevance of BTK for various diseases ranging from haematology and rheumatology to the COVID-19 pandemic. Overall, BTK signalling and its targetable nature have emerged as immensely important for a wide range of clinical applications. The development of novel, more specific and less toxic BTK inhibitors could be revolutionary for a significant number of diseases with yet unmet treatment needs.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/metabolism , B-Lymphocytes/enzymology , Immune System/enzymology , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Animals , Autoimmune Diseases/drug therapy , Autoimmune Diseases/enzymology , Autoimmune Diseases/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , COVID-19/drug therapy , COVID-19/enzymology , COVID-19/immunology , Humans , Immune System/drug effects , Immune System/immunology , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/enzymology , Lymphoproliferative Disorders/immunology , Molecular Targeted Therapy , Protein Kinase Inhibitors/therapeutic use , Receptors, Antigen, B-Cell/metabolism , Receptors, Chemokine/metabolism , Signal Transduction , Toll-Like Receptors/metabolism
12.
Sci Rep ; 11(1): 21075, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1493212

ABSTRACT

Bats are potential natural reservoirs for emerging viruses, causing deadly human diseases, such as COVID-19, MERS, SARS, Nipah, Hendra, and Ebola infections. The fundamental mechanisms by which bats are considered "living bioreactors" for emerging viruses are not fully understood. Some studies suggest that tolerance to viruses is linked to suppressing antiviral immune and inflammatory responses due to DNA damage by energy generated to fly. Our study reveals that bats' gut bacteria could also be involved in the host and its microbiota's DNA damage. We performed screening of lactic acid bacteria and bacilli isolated from bats' feces for mutagenic and oxidative activity by lux-biosensors. The pro-mutagenic activity was determined when expression of recA increased with the appearance of double-strand breaks in the cell DNA, while an increase of katG expression in the presence of hydroxyl radicals indicated antioxidant activity. We identified that most of the isolated bacteria have pro-mutagenic and antioxidant properties at the same time. This study reveals new insights into bat gut microbiota's potential involvement in antiviral response and opens new frontiers in preventing emerging diseases originating from bats.


Subject(s)
Chiroptera/virology , Gastrointestinal Microbiome , Mutagens , Animals , Antioxidants/metabolism , Antiviral Agents , Bacillus , Bacterial Proteins/genetics , Biosensing Techniques , COVID-19 , DNA , DNA Damage , Disease Reservoirs/virology , Escherichia coli/metabolism , Feces , Immune System , Inflammation , Lactic Acid/metabolism , Mass Spectrometry , Mutagenesis , Oxidative Stress , Rec A Recombinases/metabolism , SARS-CoV-2 , Viruses/isolation & purification , Zoonoses/virology
13.
Cell Transplant ; 30: 9636897211049814, 2021.
Article in English | MEDLINE | ID: covidwho-1484237

ABSTRACT

During the past 18 months as the world dealt with the COVID-19 pandemic, articles published in Cell Transplantation (CT) voiced unique perspectives on the disease which have since been supported by additional research. Intrigued by the variability in COVID-19 severity, CT authors explored the influence of variants in angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) genes, as well as the role of androgen receptors on disease development. Mesenchymal stem cells (MSC) were offered up as a potential COVID-19 therapy because of their immune modulating characteristics and successful use in other acute respiratory diseases. Two CT author groups gave proof of principle when hospitalized COVID-19 patients were infused with MSC after no other interventions seemed to work. MSC treatment reduced disease severity and shortened hospitalization stays. Lastly, CT authors speculated why we are still in the midst of a pandemic and the consequences of disillusioned comfort as we face new emerging variants that may undermine all we have accomplished thus far.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Mesenchymal Stem Cells/cytology , Serine Endopeptidases/genetics , Angiotensin-Converting Enzyme 2/metabolism , Biomedical Research , Cell Transplantation , Cytokines/metabolism , Hospitalization , Humans , Immune System , Mesenchymal Stem Cells/metabolism , Peptidyl-Dipeptidase A/genetics , Publications , Receptors, Androgen/metabolism , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
14.
Sci Rep ; 11(1): 20715, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1479810

ABSTRACT

The current COVID-19 pandemic has created unmeasurable damages to society at a global level, from the irreplaceable loss of life, to the massive economic losses. In addition, the disease threatens further biodiversity loss. Due to their shared physiology with humans, primates, and particularly great apes, are susceptible to the disease. However, it is still uncertain how their populations would respond in case of infection. Here, we combine stochastic population and epidemiological models to simulate the range of potential effects of COVID-19 on the probability of extinction of mountain gorillas. We find that extinction is sharply driven by increases in the basic reproductive number and that the probability of extinction is greatly exacerbated if the immunity lasts less than 6 months. These results stress the need to limit exposure of the mountain gorilla population, the park personnel and visitors, as well as the potential of vaccination campaigns to extend the immunity duration.


Subject(s)
Ape Diseases/epidemiology , Ape Diseases/physiopathology , COVID-19/epidemiology , COVID-19/physiopathology , Animals , Animals, Newborn , COVID-19/veterinary , Computer Simulation , Endangered Species , Female , Gorilla gorilla , Immune System , Male , Models, Statistical , Pandemics , Probability , SARS-CoV-2 , Stochastic Processes
15.
Int J Mol Sci ; 22(20)2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1477961

ABSTRACT

Chronic diseases and viral infections have threatened human life over the ages and constitute the main reason for increasing death globally. The rising burden of these diseases extends to negatively affecting the economy and trading globally, as well as daily life, which requires inexpensive, novel, and safe therapeutics. Therefore, scientists have paid close attention to probiotics as safe remedies to combat these morbidities owing to their health benefits and biotherapeutic effects. Probiotics have been broadly adopted as functional foods, nutraceuticals, and food supplements to improve human health and prevent some morbidity. Intriguingly, recent research indicates that probiotics are a promising solution for treating and prophylactic against certain dangerous diseases. Probiotics could also be associated with their essential role in animating the immune system to fight COVID-19 infection. This comprehensive review concentrates on the newest literature on probiotics and their metabolism in treating life-threatening diseases, including immune disorders, pathogens, inflammatory and allergic diseases, cancer, cardiovascular disease, gastrointestinal dysfunctions, and COVID-19 infection. The recent information in this report will particularly furnish a platform for emerging novel probiotics-based therapeutics as cheap and safe, encouraging researchers and stakeholders to develop innovative treatments based on probiotics to prevent and treat chronic and viral diseases.


Subject(s)
Chronic Disease/therapy , Probiotics/administration & dosage , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/therapy , Fatty Acids, Volatile/metabolism , Gastrointestinal Microbiome , Humans , Immune System/metabolism , Inflammation/metabolism , Inflammation/pathology , Neoplasms/metabolism , Neoplasms/therapy , Virus Diseases/immunology , Virus Diseases/metabolism , Virus Diseases/therapy
16.
Int J Mol Sci ; 22(20)2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1477960

ABSTRACT

A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.


Subject(s)
COVID-19/pathology , Lung/physiology , Regeneration , COVID-19/virology , Epigenomics , Fibrosis , Humans , Immune System/metabolism , MicroRNAs/metabolism , SARS-CoV-2/isolation & purification , Signal Transduction
17.
Biol Direct ; 16(1): 18, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1477451

ABSTRACT

Skeletal muscle has an extraordinary regenerative capacity reflecting the rapid activation and effective differentiation of muscle stem cells (MuSCs). In the course of muscle regeneration, MuSCs are reprogrammed by immune cells. In turn, MuSCs confer immune cells anti-inflammatory properties to resolve inflammation and facilitate tissue repair. Indeed, MuSCs can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory ability, including effects primed by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). At the molecular level, the tryptophan metabolites, kynurenine or kynurenic acid, produced by indoleamine 2,3-dioxygenase (IDO), augment the expression of TNF-stimulated gene 6 (TSG6) through the activation of the aryl hydrocarbon receptor (AHR). In addition, insulin growth factor 2 (IGF2) produced by MuSCs can endow maturing macrophages oxidative phosphorylation (OXPHOS)-dependent anti-inflammatory functions. Herein, we summarize the current understanding of the immunomodulatory characteristics of MuSCs and the issues related to their potential applications in pathological conditions, including COVID-19.


Subject(s)
COVID-19/therapy , Immune System/physiology , Muscles/physiology , Regeneration/physiology , Stem Cells/cytology , Animals , COVID-19/immunology , Cell Adhesion Molecules/metabolism , Cell Differentiation , Cell Proliferation , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Inflammation , Insulin-Like Growth Factor II/metabolism , Interferon-gamma/metabolism , Kynurenic Acid/metabolism , Kynurenine/metabolism , Macrophages/metabolism , Mice , Muscles/metabolism , Oxidative Phosphorylation , Receptors, Aryl Hydrocarbon/metabolism , Tryptophan/chemistry , Tumor Necrosis Factor-alpha/metabolism
18.
Cells ; 10(10)2021 10 14.
Article in English | MEDLINE | ID: covidwho-1470798

ABSTRACT

Basophils and mast cells are among the principal inducers of Th2 responses and have a crucial role in allergic and anti-parasitic protective immunity. Basophils can function as antigen-presenting cells that bind antigens on their surface and boost humoral immune responses, inducing Th2 cell differentiation. Their depletion results in lower humoral memory activation and greater infection susceptibility. Basophils seem to have an active role upon immune response to SARS-CoV-2. In fact, a coordinate adaptive immune response to SARS-CoV-2 is magnified by basophils. It has been observed that basophil amount is lower during acute disease with respect to the recovery phase and that the grade of this depletion is an important determinant of the antibody response to the virus. Moreover, mast cells, present in a great quantity in the nasal epithelial and lung cells, participate in the first immune response to SARS-CoV-2. Their activation results in a hyperinflammatory syndrome through the release of inflammatory molecules, participating to the "cytokine storm" and, in a longer period, inducing pulmonary fibrosis. The literature data suggest that basophil counts may be a useful prognostic tool for COVID-19, since their reduction is associated with a worse prognosis. Mast cells, on the other hand, represent a possible therapeutic target for reducing the airway inflammation characteristic of the hyperacute phase of the disease.


Subject(s)
Basophils/cytology , COVID-19/immunology , COVID-19/physiopathology , Mast Cells/cytology , Adaptive Immunity , Animals , COVID-19/blood , Cell Differentiation , Cytokines/metabolism , Granulocytes/cytology , Humans , Hypersensitivity/metabolism , Immune System , Immunity, Humoral , Immunity, Innate , Inflammation , Macrophages/cytology , Mice , SARS-CoV-2 , Th17 Cells/cytology , Th2 Cells/cytology
19.
Expert Rev Gastroenterol Hepatol ; 15(11): 1281-1294, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1470080

ABSTRACT

INTRODUCTION: Human gut microbiota plays a crucial role in providing protective responses against pathogens, particularly by regulating immune system homeostasis. There is a reciprocal interaction between the gut and lung microbiota, called the gut-lung axis (GLA). Any alteration in the gut microbiota or their metabolites can cause immune dysregulation, which can impair the antiviral activity of the immune system against respiratory viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. AREAS COVERED: This narrative review mainly outlines emerging data on the mechanisms underlying the interactions between the immune system and intestinal microbial dysbiosis, which is caused by an imbalance in the levels of essential metabolites. The authors will also discuss the role of probiotics in restoring the balance of the gut microbiota and modulation of cytokine storm. EXPERT OPINION: Microbiota-derived signals regulate the immune system and protect different tissues during severe viral respiratory infections. The GLA's equilibration could help manage the mortality and morbidity rates associated with SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , Dysbiosis/immunology , Gastrointestinal Microbiome/immunology , Immune System/immunology , Pneumonia, Viral/immunology , Humans , SARS-CoV-2
20.
Lab Anim (NY) ; 50(10): 285-294, 2021 10.
Article in English | MEDLINE | ID: covidwho-1467139

ABSTRACT

Enchytraeids (Annelida) are soil invertebrates with worldwide distribution that have served as ecotoxicology models for over 20 years. We present the first high-quality reference genome of Enchytraeus crypticus, assembled from a combination of Pacific Bioscience single-molecule real-time and Illumina sequencing platforms as a 525.2 Mbp genome (910 gapless scaffolds and 18,452 genes). We highlight isopenicillin, acquired by horizontal gene transfer and conferring antibiotic function. Significant gene family expansions associated with regeneration (long interspersed nuclear elements), the innate immune system (tripartite motif-containing protein) and response to stress (cytochrome P450) were identified. The ACE (Angiotensin-converting enzyme) - a homolog of ACE2, which is involved in the coronavirus SARS-CoV-2 cell entry - is also present in E. crypticus. There is an obvious potential of using E. crypticus as a model to study interactions between regeneration, the innate immune system and aging-dependent decline.


Subject(s)
COVID-19 , Oligochaeta , Animals , Humans , Immune System , Oligochaeta/genetics , SARS-CoV-2 , Soil
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