scholarly journals Pericentromeric hypomethylation elicits an interferon response in an animal model of ICF syndrome

2018 ◽  
Author(s):  
Srivarsha Rajshekar ◽  
Jun Yao ◽  
Paige K. Arnold ◽  
Sara G. Payne ◽  
Yinwen Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Animal Model ◽  
Innate Immune System ◽  
Innate Immune ◽  
Interferon Response ◽  
Wild Type ◽  
Icf Syndrome ◽  
Progressive Loss ◽  
Satellite Repeats ◽  
General Importance

AbstractPericentromeric satellite repeats are enriched in 5-methylcytosine (5mC). Loss of 5mC at these sequences is common in cancer and is a hallmark of Immunodeficiency, Centromere and Facial abnormalities (ICF) syndrome. While the general importance of 5mC is well-established, the specific functions of 5mC at pericentromeres are less clear. To address this deficiency, we generated a viable animal model of pericentromeric hypomethylation through mutation of the ICF-gene ZBTB24. Deletion of zebrafish zbtb24 caused a progressive loss of 5mC at pericentromeres and ICF-like phenotypes. Hypomethylation of these repeats triggered derepression of pericentromeric transcripts and activation of an interferon-based innate immune response. Injection of pericentromeric RNA is sufficient to elicit this response in wild-type embryos, and mutation of the MDA5-MAVS dsRNA-sensing machinery blocks the response in mutants. These findings identify activation of the innate immune system as an early consequence of pericentromeric hypomethylation, implicating derepression of pericentromeric transcripts as a trigger of autoimmunity.

scholarly journals Pericentromeric hypomethylation elicits an interferon response in an animal model of ICF syndrome

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Srivarsha Rajshekar ◽  
Jun Yao ◽  
Paige K Arnold ◽  
Sara G Payne ◽  
Yinwen Zhang ◽  
...  
Keyword(s):  
Animal Model ◽  
Innate Immune System ◽  
Innate Immune ◽  
Interferon Response ◽  
Editorial Note ◽  
Wild Type ◽  
Icf Syndrome ◽  
Progressive Loss ◽  
Satellite Repeats ◽  
General Importance

Pericentromeric satellite repeats are enriched in 5-methylcytosine (5mC). Loss of 5mC at these sequences is common in cancer and is a hallmark of Immunodeficiency, Centromere and Facial abnormalities (ICF) syndrome. While the general importance of 5mC is well-established, the specific functions of 5mC at pericentromeres are less clear. To address this deficiency, we generated a viable animal model of pericentromeric hypomethylation through mutation of the ICF-gene ZBTB24. Deletion of zebrafish zbtb24 caused a progressive loss of 5mC at pericentromeres and ICF-like phenotypes. Hypomethylation of these repeats triggered derepression of pericentromeric transcripts and activation of an interferon-based innate immune response. Injection of pericentromeric RNA is sufficient to elicit this response in wild-type embryos, and mutation of the MDA5-MAVS dsRNA-sensing machinery blocks the response in mutants. These findings identify activation of the innate immune system as an early consequence of pericentromeric hypomethylation, implicating derepression of pericentromeric transcripts as a trigger of autoimmunity.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

scholarly journals Insights into Innate Immune Response Against SARS-CoV-2 Infection

2021 ◽  
Vol 29 (3) ◽  
pp. 255-269
Author(s):  
Adina Huțanu ◽  
Anca Meda Georgescu ◽  
Akos Vince Andrejkovits ◽  
William Au ◽  
Minodora Dobreanu
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Innate Immune System ◽  
Time Course ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Response ◽  
Humoral Factors ◽  
Key Steps

Abstract The innate immune system is mandatory for the activation of antiviral host defense and eradication of the infection. In this regard, dendritic cells, natural killer cells, macrophages, neutrophils representing the cellular component, and cytokines, interferons, complement or Toll-Like Receptors, representing the mediators of unspecific response act together for both activation of the adaptive immune response and viral clearance. Of great importance is the proper functioning of the innate immune response from the very beginning. For instance, in the early stages of viral infection, the defective interferon response leads to uncontrolled viral replication and pathogen evasion, while hypersecretion during the later stages of infection generates hyperinflammation. This cascade activation of systemic inflammation culminates with cytokine storm syndrome and hypercoagulability state, due to a close interconnection between them. Thus an unbalanced reaction, either under- or over- stimulation of the innate immune system will lead to an uncoordinated response and unfavorable disease outcomes. Since both cellular and humoral factors are involved in the time-course of the innate immune response, in this review we aimed to address their gradual involvement in the antiviral response with emphasis on key steps in SARS-CoV-2 infection.

scholarly journals Multiple Roles of Myd88 in the Immune Response to the Plague F1-V Vaccine and in Protection against an Aerosol Challenge ofYersinia pestisCO92 in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Jennifer L. Dankmeyer ◽  
Randy L. Fast ◽  
Christopher K. Cote ◽  
Patricia L. Worsham ◽  
David Fritz ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune System ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Multiple Roles ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Lethal Challenge ◽  
V Protein ◽  
Deficient Mice

The current candidate vaccine againstYersinia pestisinfection consists of two subunit proteins: the capsule protein or F1 protein and the low calcium response V protein or V-antigen. Little is known of the recognition of the vaccine by the host’s innate immune system and how it affects the acquired immune response to the vaccine. Thus, we vaccinated Toll-like receptor (Tlr)2,4, and2/4-double deficient, as well as signal adaptor proteinMyd88-deficient mice. We found that Tlr4 and Myd88 appeared to be required for an optimal immune response to the F1-V vaccine but not Tlr2 when compared to wild-type mice. However, there was a difference between the requirement for Tlr4 and MyD88 in vaccinated animals. When F1-V vaccinatedTlr4mutant (lipopolysaccharide tolerant) andMyd88-deficient mice were challenged by aerosol withY. pestisCO92, all but oneTlr4mutant mice survived the challenge, but no vaccinatedMyd88-deficient mice survived the challenge. Spleens from these latter nonsurviving mice showed thatY. pestiswas not cleared from the infected mice. Our results suggest that MyD88 appears to be important for both an optimal immune response to F1-V and in protection against a lethal challenge ofY. pestisCO92 in F1-V vaccinated mice.

scholarly journals SARS CoV-2 Might Exploit Cells of the Innate Immune System to Induce the Novel Acute Immune Dysrhythmic Syndrome (n-AIDS) and Para COVID-19 Syndrome.

2021 ◽  
Author(s):  
Mina Kelleni
Keyword(s):  
Immune Response ◽  
Innate Immune System ◽  
Langerhans Cells ◽  
Interesting Case ◽  
Innate Immune ◽  
Delayed Type Hypersensitivity ◽  
The Novel ◽  
Cytokine Storm ◽  
Humoral Immune ◽  
Cytokines And Chemokines

In this manuscript, we combine our insights towards COVID-19 to present a hypothesis that might explain its pathogenesis and complications while presenting an interesting case report of post COVID-19 allergic cell mediated (dysregulated) delayed type hypersensitivity. Moreover, we confirm our call to reclassify it as novel acute immune dysrhythmic syndrome (n-AIDS) to include both cytokine storm and we suggest to describe post or long COVID and other autoimmune complications as para COVID-19 syndrome. We suggest that SARS CoV-2 might exploit monocytes, macrophages and tissue resident macrophages including skin Langerhans cells to induce dysregulated cellular and humoral immune response through known and yet to be discovered cytokines and chemokines to ultimately induce the cytokine storm and/or autoimmune responses.

scholarly journals A novel animal model for neuroinflammation and white matter degeneration

2017 ◽  
Author(s):  
Baohu Ji ◽  
Kerin Higa ◽  
Virawudh Soontornniyomkij ◽  
Atsushi Miyanohara ◽  
Xianjin Zhou
Keyword(s):  
Animal Model ◽  
Immune System ◽  
White Matter ◽  
Innate Immune System ◽  
D1 Receptor ◽  
Innate Immune ◽  
Small Interference Rna ◽  
Cell Defense ◽  
White Matter Degeneration ◽  
Short Hairpin Rnas

Small interference RNA has been widely used to suppress gene expression. Three different short-hairpin RNAs (shRNAs) against dopamine D1 receptor (Drd1), driven by mouse U6 promoter in self-complementary AAV8 vector (scAAV8), were used to silence mouse striatal Drd1 expression. Transduction of mouse striatum with all 3 scAAV8-D1shRNA virus, but not the control scAAV8 virus, causes extensive neuroinflammation, demyelination, and axon degeneration. RNA interference is known to be coupled to the innate immune system as a host cell defense against virus infection. Activation of the innate immune system may play a causal role in the development of neuroinflammation and white matter degeneration, providing a novel animal model for multiple sclerosis (MS) and other neuroinflammatory diseases.

RNA sensors as a mechanism of innate immune evasion among SARS-CoV2, HIV and Nipah viruses

2021 ◽  
Vol 22 ◽  
Author(s):  
Dalia Cicily Kattiparambil Dixon ◽  
Chameli Ratan ◽  
Bhagyalakshmi Nair ◽  
Sabitha Mangalath ◽  
Rachy Abraham ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Vaccine Development ◽  
Innate Immune ◽  
Interferon Response ◽  
Host Immune System ◽  
Type I ◽  
Adaptive Responses ◽  
Rna Sensors

: Innate immunity is the first line of defence elicited by the host immune system to fight against invading pathogens such as viruses and bacteria. From this elementary immune response, the more complex antigen-specific adaptive responses are recruited to provide a long-lasting memory against the pathogens. Innate immunity gets activated when the host cell utilizes a diverse set of receptors known as pattern recognition receptors (PRR) to recognize the viruses that have penetrated the host and respond with cellular processes like complement system, phagocytosis, cytokine release and inflammation and destruction of NK cells. Viral RNA or DNA or viral intermediate products are recognized by receptors like toll-like receptors(TLRs), nucleotide oligomerization domain(NOD)-like receptors (NLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) thereby, inducing type I interferon response (IFN) and other proinflammatory cytokines in infected cells or other immune cells. But certain viruses can evade the host innate immune response to replicate efficiently, triggering the spread of the viral infection. The present review describes the similarity in the mechanism chosen by viruses from different families -HIV, SARS-CoV2 and Nipah viruses to evade the innate immune response and how efficiently they establish the infection in the host. The review also addresses the stages of developments of various vaccines against these viral diseases and the challenges encountered by the researchers during vaccine development.

scholarly journals Insights into Sensing of Murine Retroviruses

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 836
Author(s):  
Eileen A. Moran ◽  
Susan R. Ross
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nucleic Acid ◽  
Adaptive Immunity ◽  
Innate Immune System ◽  
Innate Immune ◽  
Genetic Tool ◽  
Causes Of Disease ◽  
Retrovirus Infection ◽  
Insight Into

Retroviruses are major causes of disease in animals and human. Better understanding of the initial host immune response to these viruses could provide insight into how to limit infection. Mouse retroviruses that are endemic in their hosts provide an important genetic tool to dissect the different arms of the innate immune system that recognize retroviruses as foreign. Here, we review what is known about the major branches of the innate immune system that respond to mouse retrovirus infection, Toll-like receptors and nucleic acid sensors, and discuss the importance of these responses in activating adaptive immunity and controlling infection.

scholarly journals Phenoloxidase activity and haemolymph cytology in honeybees challenged with a virus suspension (deformed wings virus DWV) or phosphate buffered suspension (PBS)

2019 ◽  
Vol 49 (2) ◽  
Author(s):  
Francesca Millanta ◽  
Simona Sagona ◽  
Maurizio Mazzei ◽  
Mario Forzan ◽  
Alessandro Poli ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Innate Immune System ◽  
Innate Immune ◽  
Additional Stress ◽  
Varroa Mite ◽  
Virus Suspension ◽  
Phenoloxidase Activity ◽  
Cell Immunity

ABSTRACT: The innate immune system of honeybees mainly consists in antimicrobial peptides, cellular immunity and melanisation. In order to investigate the immune response of honeybees to immune stressors, three stress degrees were tested. Newly emerged bees naturally DWV-infected were collected from a Varroa mite-free apiary and divided into three experimental groups: naturally DWV infected bees, PBS injected bees, and artificially DWV super infected bees. Phenoloxidase activity and haemolymph cellular subtype count were investigated. Phenoloxidase activity was highest (P<0.05) in DWV-superinfected bees, and the haemocyte population differed within the three observed groups. Although, immune responses following DWV infection have still not been completely clarified, this investigation sheds light on the relation between cell immunity and the phenoloxidase activity of DWV-naturally infected honeybees exposed to additional stress such as injury and viral superinfection.

scholarly journals P53 and The Immune Response: 40 Years of Exploration—A Plan for the Future

2020 ◽  
Vol 21 (2) ◽  
pp. 541 ◽  
Author(s):  
Arnold J. Levine
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
P53 Protein ◽  
P53 Gene ◽  
T Cell Response ◽  
Innate Immune ◽  
Transplantation Antigen ◽  
Mutant Form ◽  
The Future

The p53 field was born from a marriage of the techniques of cancer virus research and immunology. Over the past 40 years, it has followed the path of cancer research. Now cancer treatments are turning to immunotherapy, and there are many hints of the role of the p53 protein in both the regulation of the innate immune system and as an antigen in adaptive immune responses. The p53 gene and protein are part of the innate immune system, and play an important role in infectious diseases, senescence, aging, and the surveillance of repetitive DNA and RNAs. The mutant form of the p53 protein in cancers elicits both a B-cell antibody response (a tumor antigen) and a CD-8 killer T-cell response (a tumor-specific transplantation antigen). The future will take the p53-immune response field of research into cancer immunotherapy, autoimmunity, inflammatory responses, neuro-degeneration, aging, and life span, and the regulation of epigenetic stability and tissue regeneration. The next 40 years will bring the p53 gene and its proteins out of a cancer focus and into an organismic and environmental focus.

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