scholarly journals BIOINFORMATIC SEARCH OF CRISPR/CAS SYSTEM STRUCTURES IN GENOME OF PCT281 PLASMID OF BACILLUS THURINGIENSIS SUBSP. CHINENSIS STRAIN CT-43

2018 ◽  
Vol 3 (5) ◽  
pp. 33-38
Author(s):  
N. A. Arefyeva ◽  
Yu. P. Dzhioev ◽  
A. Yu. Borisenko ◽  
V. I. Chemerilova ◽  
O. F. Vyatchina ◽  
...  
Keyword(s):  
Bacillus Thuringiensis ◽  
Bacterial Genome ◽  
Repeat Sequence ◽  
Immune Defense ◽  
System Structure ◽  
Type I ◽  
Adaptive Immune ◽  
Bacillus Thuringiensis Subsp ◽  
New Information

Background.CRISPR/Cas systems loci are one of the functionally important patterns in bacterial genome which perform the role of “adaptive immune defense” from foreign nucleic acids. The study of CRISPR/Cas systems structure in genomes of plasmids and phages provide new information about the evolution of this systems in bacterial hosts.Aims.A search of CRISPR/Cas systems structures in pCT281 plasmid from Bacillus thuringiensis subsp. chinensis strain CT-43 using bioinformatic methods.Materials and methods.Search studies using bioinformatics methods were performed with the genome of pCT281 plasmid of B. thuringiensis subsp. chinensis strain CT-43 from the RefSeq database. To search for the CRISPR/Cas system structure MacSyFinder (ver. 1.0.5) and three combined algorithms were used: CRISPRFinder; PILER-CR; CRISPR Recognition Tool (CRT). The consensus repeat sequence was generated in WebLogo 3.Results and discussion.In pCT281 plasmid we detected one locus of CRISPR/Cas system of the type I-C which contains 2 CRISPR-cassettes and 4 cas-genes located between them. The CRISPR-cassette 1 includes 10 spacers from 32 to 35 bp and 11 repeats 32bp in length. 5 spacers (33–35 bp) separated by 6 repeats 32 bp in length were detected in the CRISPR-cassette 2.Conclusions.The bioinformatic methods used in this study enable to conduct a search of CRISPR/Cas systems structures in plasmid genomes. The presence of the CRISPR-Cas locus in pCT281 plasmid confirms a possible transfer of this system from the nucleoid to this plasmid. The detected spacers provide information about phages this bacteria was encountered.

scholarly journals Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3090
Author(s):  
Toshimasa Shimizu ◽  
Hideki Nakamura ◽  
Atsushi Kawakami
Keyword(s):  
Immune Responses ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Adaptive Immune ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

scholarly journals Type I Interferons Mediate the Innate Cytokine Response to Recombinant Fowlpox Virus but Not the Induction of Plasmacytoid Dendritic Cell-Dependent Adaptive Immunity

2010 ◽  
Vol 84 (13) ◽  
pp. 6549-6563 ◽  
Author(s):  
Erin L. Lousberg ◽  
Cara K. Fraser ◽  
Michael G. Tovey ◽  
Kerrilyn R. Diener ◽  
John D. Hayball
Keyword(s):  
Immune Responses ◽  
Plasmacytoid Dendritic Cell ◽  
Type I Interferons ◽  
Interleukin 12 ◽  
Type I ◽  
Adaptive Immune Responses ◽  
Fowlpox Virus ◽  
Adaptive Immune ◽  
Type I Ifns

ABSTRACT Type I interferons (IFNs) are considered to be important mediators of innate immunity due to their inherent antiviral activity, ability to drive the transcription of a number of genes involved in viral clearance, and their role in the initiation of innate and adaptive immune responses. Due to the central role of type I IFNs, we sought to determine their importance in the generation of immunity to a recombinant vaccine vector fowlpox virus (FPV). In analyzing the role of type I IFNs in immunity to FPV, we show that they are critical to the secretion of a number of innate and proinflammatory cytokines, including type I IFNs themselves as well as interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-α), IL-6, and IL-1β, and that deficiency leads to enhanced virus-mediated antigen expression. Interestingly, however, type I IFNs were not required for adaptive immune responses to recombinant FPV even though plasmacytoid dendritic cells (pDCs), the primary producers of type I IFNs, have been shown to be requisite for this to occur. Furthermore, we provide evidence that the importance of pDCs may lie in their ability to capture and present virally derived antigen to T cells rather than in their capacity as professional type I IFN-producing cells.

The innate immune system in human systemic lupus erythematosus

2017 ◽  
Vol 131 (8) ◽  
pp. 625-634 ◽  
Author(s):  
Marc Weidenbusch ◽  
Onkar P. Kulkarni ◽  
Hans-Joachim Anders
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Innate Immune System ◽  
Innate Immune ◽  
Type I ◽  
Human Systemic Lupus Erythematosus ◽  
Systemic Lupus ◽  
Adaptive Immune

Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized. An intricate interplay between both innate and adaptive immune elements exists in protective anti-infective immunity as well as in detrimental autoimmunity. More recently, it has become clear that the innate immune system in this regard not only starts inflammation cascades in SLE leading to disease flares, but also continues to fuel adaptive immune responses throughout the course of the disease. This is why targeting the innate immune system offers an additional means of treating SLE. First trials assessing the efficacy of anti-type I interferon (IFN) therapy or modulators of pattern recognition receptor (PRR) signalling have been attempted. In this review, we summarize the available evidence on the role of several distinct innate immune elements, especially neutrophils and dendritic cells as well as the IFN system, as well as specific innate PRRs along with their signalling pathways. Finally, we highlight recent clinical trials in SLE addressing one or more of the aforementioned components of the innate immune system.

scholarly journals Role of Type I Interferons on Filovirus Pathogenesis

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 22 ◽  
Author(s):  
Beatriz Escudero-Pérez ◽  
César Muñoz-Fontela
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Marburg Virus ◽  
Type I Interferons ◽  
Type I ◽  
Adaptive Immune ◽  
Antigen Presenting

Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and bystander cells, and impair the ability of antigen-presenting cells to initiate adaptive immune responses. However, in recent years, a number of studies have underscored the conflicting data between in vitro studies and in vivo data obtained in animal models and clinical studies during outbreaks. This review aims to summarize these data and to discuss the relative contributions of IFN-α and IFN-β to filovirus pathogenesis in animal models and humans. Finally, we evaluate the putative utilization of IFN-I in post-exposure therapy and its implications as a biomarker of vaccine efficacy.

scholarly journals Tweaking Innate Immunity: The Promise of Innate Immunologicals as Anti-Infectives

2006 ◽  
Vol 17 (5) ◽  
pp. 307-314 ◽  
Author(s):  
Kenneth L Rosenthal
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Immune Responses ◽  
Innate Immune System ◽  
Immune Defense ◽  
Innate Immune ◽  
Parasitic Infections ◽  
Type I ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs) to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs) are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as 'innate immunologicals') can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.

scholarly journals Type I-E CRISPR-Cas system as an immune system in a eukaryote

2018 ◽  
Author(s):  
Devashish Rath ◽  
Lina Amlinger ◽  
Gargi Bindal ◽  
Magnus Lundgren
Keyword(s):  
Nucleic Acid ◽  
Dna Cleavage ◽  
Basic Research ◽  
Type I ◽  
Crispr Locus ◽  
Adaptive Immune ◽  
Research Platform ◽  
Adaptive Immune Systems ◽  
Cas Proteins

AbstractDefense against viruses and other mobile genetic elements (MGEs) is important in many organisms. The CRISPR-Cas systems found in bacteria and archaea constitute adaptive immune systems that acquire the ability to recognize MGEs by introducing nucleic acid samples, spacers, in the CRISPR locus. The CRISPR is transcribed and processed, and the produced CRISPR RNAs guide Cas proteins to degrade matching nucleic acid sequences. No CRISPR-Cas system is found to occur naturally in eukaryotic cells but here we demonstrate interference by type I-E CRISPR-Cas system from Escherichia coli introduced in Saccharomyces cerevisiae. The designed CRISPR arrays are properly expressed and processed in S. cerevisiae. Targeted plasmids display reduced transformation efficiency, indicative of DNA cleavage. Unlike e.g. Cas9-based systems, which can be used to inactivate MGEs in eukaryotes by introducing specific mutations, type I-E systems processively degrade the target. The type I-E system thus allows for defense without knowledge of MGE gene function. The reconstituted CRISPR-Cas system in S. cerevisiae can also function as a basic research platform for testing the role of various factors in the interference process.

scholarly journals Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes

2017 ◽  
Vol 214 (6) ◽  
pp. 1769-1785 ◽  
Author(s):  
Silvia Cerboni ◽  
Nadia Jeremiah ◽  
Matteo Gentili ◽  
Ulf Gehrmann ◽  
Cécile Conrad ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Inflammatory Gene Expression ◽  
Adaptive Immune ◽  
Cyclic Dinucleotide

Activation of the cyclic dinucleotide sensor stimulator of interferon (IFN) genes (STING) is critical for IFN and inflammatory gene expression during innate immune responses. However, the role of STING in adaptive immunity is still unknown. In this study, we show that STING activation reduces the proliferation of T lymphocytes. This activity was independent of TBK1 and IRF3 recruitment and of type I IFN but required a distinct C-terminal domain of STING that activates NF-κB. Inhibition of cell proliferation by STING required its relocalization to the Golgi apparatus and caused mitotic errors. T lymphocytes from patients carrying constitutive active mutations in TMEM173 encoding STING showed impaired proliferation and reduced numbers of memory cells. Endogenous STING inhibited proliferation of mouse T lymphocytes. Therefore, STING, a critical innate sensor, also functions intrinsically in cells of the adaptive immune system to inhibit proliferation.

Isolation, Characterization and Biological Role of Camelysin from Bacillus thuringiensis Subsp. israelensis

2010 ◽  
Vol 61 (3) ◽  
pp. 176-183 ◽  
Author(s):  
Marina Nisnevitch ◽  
Sasi Sigawi ◽  
Rivka Cahan ◽  
Yeshayahu Nitzan
Keyword(s):  
Bacillus Thuringiensis ◽  
Biological Role ◽  
Bacillus Thuringiensis Subsp

scholarly journals The Role of Type I IFNs in Influenza: Antiviral Superheroes or Immunopathogenic Villains?

2020 ◽  
Vol 12 (6) ◽  
pp. 437-447 ◽  
Author(s):  
Wenxin Wu ◽  
Jordan P. Metcalf
Keyword(s):  
Influenza A ◽  
Cell Function ◽  
Influenza Infection ◽  
Immune Defense ◽  
Type I ◽  
Type I Ifns ◽  
Infection Treatment ◽  
Individual Host ◽  
The Individual

The important role of interferons (IFNs) in antiviral innate immune defense is well established. Although recombinant IFN-α was approved for cancer and chronic viral infection treatment by regulatory agencies in many countries starting in 1986, no IFNs are approved for treatment of influenza A virus (IAV) infection. This is partially due to the complex effects of IFNs in acute influenza infection. IAV attacks the human respiratory system and causes significant morbidity and mortality globally. During influenza infection, depending on the strain of IAV and the individual host, type I IFNs can have protective antiviral effects or can contribute to immunopathology. In the context of virus infection, the immune system has complicated mechanisms regulating the expression and effects of type I IFN to maximize the antiviral response by both activating and enhancing beneficial innate cell function, while limiting immunopathological responses that lead to exaggerated tissue damage. In this review, we summarize the complicated, but important, role of type I IFNs in influenza infections. This includes both protective and harmful effects of these important cytokines during infection.

scholarly journals Physiological Role of Plasmacytoid Dendritic Cells and Their Potential Use in Cancer Immunity

2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Jorge Schettini ◽  
Pinku Mukherjee
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Tumor Antigens ◽  
Physiological Role ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Therapeutic Approaches ◽  
Adaptive Immune ◽  
Type I Ifns

Dendritic cells (DCs) play a pivotal role in the control of innate and adaptive immune responses. They are a heterogeneous cell population, where plasmacytoid dendritic cells (pDCs) are a unique subset capable of secreting high levels of type I IFNs. It has been demonstrated that pDCs can coordinate events during the course of viral infection, atopy, autoimmune diseases, and cancer. Therefore, pDC, as a main source of type I IFN, is an attractive target for therapeutic manipulations of the immune system to elicit a powerful immune response against tumor antigens in combination with other therapies. The therapeutic vaccination with antigen-pulsed DCs has shown a limited efficacy to generate an effective long-lasting immune response against tumor cells. A rational manipulation and design of vaccines which could include DC subsets outside “Langerhans cell paradigm” might allow us to improve the therapeutic approaches for cancer patients.

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