Features of immunopathogenesis of a new coronavirus infection

The main biological characteristics of viruses of the Coronaviridae family are presented. The features of the immunopathogenesis of these infections are analyzed. It was found that the structural proteins of the spine, membrane, envelope and nucleocapsid play an important role in the immunopathogenesis of COVID-19 infection. They are associated with hyperactivation of neutrophils and monocytes-macrophages, secreting large amounts of pro-inflammatory cytokines and chemokines. This contributes to the development of a cytokine storm and an unfavorable prognosis of the disease. A particularly high risk of developing pneumonia exists against the background of an increase in the production of: macrophage inflammatory protein-1 alpha, macrophage chemotactic protein, interleukin 8. At the height of infection in some patients, macrophages and dendritic cells infected with SARS-CoV-2 lose their ability to produce type I interferons and pro-inflammatory cytokines. On the part of cellular immunity, a significant decrease in the number of CD4+ and CD8+-lymphocytes was noted. Among IgG sub-isotypes, IgG3 antibodies had the highest reactivity, and IgG1 antibodies were less reactive. Antibodies to spike protein with low specificity or low titer do not neutralize the virus and contribute to the contamination of immunocompetent cells via Fc receptors. Low-affinity antibodies or their low levels can contribute to increased cell sensitivity to SARS-CoV-2 and the development of severe forms of COVID-19 disease.

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The STING1 network regulates autophagy and cell death

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00613-4 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Ruoxi Zhang ◽

Rui Kang ◽

Daolin Tang

Keyword(s):

Cell Death ◽

Mitotic Cell ◽

Therapeutic Interventions ◽

Type I Interferons ◽

Microbial Pathogens ◽

Type I ◽

Autophagic Degradation ◽

Health And Disease ◽

Shed Light ◽

Pro Inflammatory Cytokines

AbstractCell death and immune response are at the core of life. In past decades, the endoplasmic reticulum (ER) protein STING1 (also known as STING or TMEM173) was found to play a fundamental role in the production of type I interferons (IFNs) and pro-inflammatory cytokines in response to DNA derived from invading microbial pathogens or damaged hosts by activating multiple transcription factors. In addition to this well-known function in infection, inflammation, and immunity, emerging evidence suggests that the STING1-dependent signaling network is implicated in health and disease by regulating autophagic degradation or various cell death modalities (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, mitotic cell death, and immunogenic cell death [ICD]). Here, we outline the latest advances in our understanding of the regulating mechanisms and signaling pathways of STING1 in autophagy and cell death, which may shed light on new targets for therapeutic interventions.

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Associations between HBD3 and Pro-Inflammatory Cytokines in Asymptomatic Irreversible Pulpitis

Edelweiss Applied Science and Technology ◽

10.33805/2572-6978.105 ◽

2017 ◽

pp. 14-19

Author(s):

Anita Aminoshariae ◽

Mohammed Bakkar ◽

Tracey Bonfield ◽

Santosh Ghosh ◽

Thomas A Montagnese ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Normal Group ◽

Control Group ◽

Spearman Correlation ◽

Whitney Test ◽

Cytokines And Chemokines ◽

Luminex Technology ◽

Spearman Correlation Test ◽

Irreversible Pulpitis ◽

Pro Inflammatory Cytokines

Objective: The aim of this study was to investigate the levels of Human Beta Defensin (hBD) 2 and 3, chemokine and cytokine expressions between teeth endodontically diagnosed with symptomatic irreversible pulpitis (SIP), asymptomatic irreversible pulpitis (ASIP) and normal pulps. We hypothesized that there would be a correlation between hBD’s and the immunoregulatory response. Design: Pulpal samples were collected with paper points. Six samples were obtained from normal teeth, 21 from SIP, 18 from ASIP. Levels of cytokines and betadefensins were measured by Luminex technology and ELISA, respectively. Data were statistically analyzed using Kruskal-Wallis, Wilcoxon Mann-Whitney test and Spearman correlation test. Differences were considered significant at p<0.05. Results: hBD-2 levels correlated with samples obtained from patients in the ASIP group, but not in the samples obtained from patients with SIP or the control group. HBD-3 concentrations associated with all of the cytokines and chemokines in both SIP and ASIP groups. However, in the normal group, hBD-3 correlated with only TNFα, IL-8, MCP-1, IL-1β, MIP-1a, RANTES, IL-17 in normal group. When comparing control levels of hBD-2 and hBD-3 with patients samples from either the ASIP or the SIP groups, hBD-2 and hBD-3 concentrations were highest in the ASIP group. Conclusions: The hBD-2 and-3 were highly associated with the levels of the chemokines and cytokines in ASIP group. HBD-3 concentrations correlate with the levels of the chemokines and the cytokines in the SIP and ASIP groups.

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Cannabinoid Reduces Inflammatory Cytokines, Tumor Necrosis Factor-α, and Type I Interferons in Dermatomyositis In Vitro

Journal of Investigative Dermatology ◽

10.1016/j.jid.2017.05.035 ◽

2017 ◽

Vol 137 (11) ◽

pp. 2445-2447 ◽

Cited By ~ 12

Author(s):

Elizabeth S. Robinson ◽

Paul Alves ◽

Muhammad M. Bashir ◽

Majid Zeidi ◽

Rui Feng ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Inflammatory Cytokines ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Type I Interferons ◽

Type I ◽

Factor Α ◽

Necrosis Factor

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UBQLN2 Promotes the Production of Type I Interferon via the TBK1-IRF3 Pathway

Cells ◽

10.3390/cells9051205 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1205

Author(s):

Tianhong Chen ◽

Wenjuan Zhang ◽

Bo Huang ◽

Xuan Chen ◽

Cao Huang

Keyword(s):

Inflammatory Cytokines ◽

Type I Interferon ◽

Complete Loss ◽

Functional Assay ◽

Type I ◽

Dependent Manner ◽

Frontotemporal Degeneration ◽

Dose Dependent ◽

Lateral Sclerosis ◽

Pro Inflammatory Cytokines

Mutations of Ubiquilin 2 (UBQLN2) or TANK-binding kinase 1 (TBK1) are associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). However, the mechanisms whereby UBQLN2 or TBK1 mutations lead to ALS and FTD remain unclear. Here, we explored the effect of UBQLN2 on TBK1 in HEK-293T cells or in CRISPR–Cas9-mediated IRF3 and IRF7 knockout (KO) cells. We found an interaction between TBK1 and UBQLN2, which was affected by ALS/FTD-linked mutations in TBK1 or UBQLN2. Co-expression of UBQLN2 with TBK1 elevated the protein level of TBK1 as well as the phosphorylation of TBK1 and IRF3 in a UBQLN2 dose-dependent manner, and this phosphorylation was reduced by mutant UBQLN2. In addition, the cellular production of IFN1 and related pro-inflammatory cytokines was substantially elevated when UBQLN2 and TBK1 were co-expressed, which was also decreased by mutant UBQLN2. Functional assay revealed that mutant UBQLN2 significantly reduced the binding affinity of TBK1 for its partners, including IRF3, (SQSTM1)/p62 and optineurin (OPTN). Moreover, complete loss of IRF3 abolished the induction of IFN1 and related pro-inflammatory cytokines enhanced by UBQLN2 in HEK-293T cells, whereas no significant change in IRF7 knockout cells was observed. Thus, our findings suggest that UBQLN2 promotes IRF3 phosphorylation via TBK1, leading to enhanced IFN1 induction, and also imply that the dysregulated TBK1-IRF3 pathway may play a role in UBQLN2-related neurodegeneration.

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Chijabyukpi-Tang Inhibits Pro-Inflammatory Cytokines and Chemokines via the Nrf2/HO-1 Signaling Pathway in TNF-α/IFN-γ-Stimulated HaCaT Cells and Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2020.01018 ◽

2020 ◽

Vol 11 ◽

Cited By ~ 1

Author(s):

Ji-Hyun Lee ◽

Ji-Ye Lim ◽

Eun Hee Jo ◽

Hyeon Min Noh ◽

Sunggu Park ◽

...

Keyword(s):

Atopic Dermatitis ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Skin Lesions ◽

Hacat Cells ◽

Cytokines And Chemokines ◽

Tnf Α ◽

Ifn Γ ◽

Pro Inflammatory Cytokines

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Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Clinical Immunology ◽

10.1016/j.clim.2007.11.002 ◽

2008 ◽

Vol 126 (3) ◽

pp. 345-352 ◽

Cited By ~ 44

Author(s):

Jane E. Onken ◽

Paula K. Greer ◽

Brian Calingaert ◽

Laura P. Hale

Keyword(s):

Inflammatory Cytokines ◽

Cytokines And Chemokines ◽

Pro Inflammatory Cytokines

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Combating COVID-19 with Mesenchymal Stem Cell therapy

10.31219/osf.io/3ecda ◽

2020 ◽

Author(s):

Shashikant Ray ◽

Keshav Rajarshi ◽

Aroni Chatterjee

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Therapy ◽

Inflammatory Cytokines ◽

Stem Cell Therapy ◽

Rna Virus ◽

Multiple Organ ◽

Mesenchymal Stem Cell Therapy ◽

Cytokines And Chemokines ◽

Pro Inflammatory Cytokines

The world is currently facing one of its deadliest nightmares, the rise of a global pandemic called COVID-19. The disease is caused by a positive stranded RNA virus called SARS-CoV-2. The virus mainly targets the pulmonary epithelial cells as it’s initial site of infection by letting its surface spike protein interact and bind to the host ACE2 receptor. The internalization and gradual replication of the virus results in an exaggerated immune response triggering release of many pro-inflammatory cytokines and chemokines. This immune storm is responsible for multiple health hazards in the host ultimately leading to multiple organ failure. Mesenchymal stem cell therapy offers a promising approach towards mitigating the delirious effects of the infection in the COVID-19 patients. This therapy has shown to reduce the expression of pro-inflammatory cytokines as well as repair of damaged tissues in COVID-19 patients. This review has been organized to put forward all the positive aruments and implications in support of mesenchymal stem cell therapy as a necessary approach for treating COVID-19 patients.

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Activation of STING signaling pathway effectively blocks human coronavirus infection

Journal of Virology ◽

10.1128/jvi.00490-21 ◽

2021 ◽

Author(s):

Wei Liu ◽

Hanako M. Reyes ◽

June F. Yang ◽

Yize Li ◽

Kathleen M. Stewart ◽

...

Keyword(s):

Signaling Pathway ◽

Broad Spectrum ◽

Type I Interferons ◽

Type I ◽

Immune Effector ◽

Innate Immune Effector ◽

Coronavirus Infection ◽

Novel Target ◽

Sting Pathway ◽

The Impact

The COVID-19 pandemic poses a serious global health threat. The rapid global spread of SARS-CoV-2 highlights an urgent need to develop effective therapeutics for blocking SARS-CoV-2 infection and spread. Stimulator of Interferon Genes (STING) is a chief element in host antiviral defense pathways. In this study, we examined the impact of the STING signaling pathway on coronavirus infection using the HCoV-OC43 model. We found that HCoV-OC43 infection did not stimulate the STING signaling pathway, but the activation of STING signaling effectively inhibits HCoV-OC43 infection to a much greater extent than that of type I interferons (IFNs). We also discovered that IRF3, the key STING downstream innate immune effector, is essential for this anti-coronavirus activity. In addition, we found that the amidobenzimidazole (ABZI)-based human STING agonist (diABZI) robustly blocks the infection of not only HCoV-OC43 but also SARS-CoV-2. Therefore, our study identifies the STING signaling pathway as a potential therapeutic target that could be exploited for developing broad-spectrum antiviral therapeutics against multiple coronavirus strains in order to face the challenge of future coronavirus outbreaks. Importance The highly infectious and lethal SARS-CoV-2 is posing an unprecedented threat to public health. Other coronaviruses are likely to jump from a non-human animal to humans in the future. Novel broad-spectrum antiviral therapeutics are therefore needed to control known pathogenic coronaviruses such as SARS-CoV-2 and its newly mutated variants, as well as future coronavirus outbreaks. STING signaling is a well-established host defense pathway, but its role in coronavirus infection remains unclear. In the present study, we found that activation of the STING signaling pathway robustly inhibits infection of HCoV-OC43 and SARS-CoV-2. These results identified the STING pathway as a novel target for controlling the spread of known pathogenic coronaviruses as well as emerging coronavirus outbreaks.

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