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Toll-Like Receptor Activation in Immunity vs. Tolerance

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196364 Year: Pages: 75 DOI: 10.3389/978-2-88919-636-4 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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The innate immune system has evolved means to recognize and react suitably to foreign entities such as infectious agents. In many cases infectious microorganisms threaten the integrity and function of the target organs or tissues; therefore, consequent to their recognition the immune system becomes activated to ensure their elimination. Toll-like receptors (TLR) constitute a family of receptors specialized in the recognition of molecular patterns typically associated with infectious agents. Different TLRs exist, each selective for molecular entities and motifs belonging to a specific pathogen group. Consequently, it is thought that the molecular nature of invading microorganisms activates specific TLRs to drive adequate anti-infectious immunity. For instance, nucleic acid-specific, intracellular receptors (TLR3/7/8/9) are used to sense viruses and drive antiviral immunity, while other receptors (such as TLR2 and TLR4) recognize and promote immunity against bacteria, yeast, and fungi. Yet, it is becoming evident that activation of TLR pathways trigger mechanisms that not only stimulate but also regulate the immune system. For instance, TLR stimulation by viruses will drive antiviral interferon but also immunoregulatory cytokine production and regulatory T cell activation. Stimulation of TLRs by bacteria or using molecular agonists can also trigger both immune stimulatory and regulatory responses. TLR stimulation by infectious agents likely serves to activate but also control anti-infectious immunity, for instance prevent potential immunopathological tissue damage which can be caused by acute immune defense mechanisms. Previous work by us and others has shown that the immunoregulatory arm of TLR stimulation can additionally help control autoreactive processes in autoimmune disease. Hence, it is becoming established that gut commensals, which also play a crucial part in the control of autoimmune disease, establish immune regulatory mechanisms through activation of particular TLRs. In sum, it appears that TLRs are key immune players that not only stimulate but also regulate immune processes in health and disease. In this Research Topic, we wish to review the dual role of TLRs as activators and regulators of immune responses. We aim to motivate data-driven opinions as to the importance of context of TLR agonism for determining immune activation vs. regulation. The presentation of ongoing original works, as well as data and opinions around other innate immune receptors pertaining to this topic, are also encouraged.

CD1- and MR1-restricted T Cells in Antimicrobial Immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197507 Year: Pages: 189 DOI: 10.3389/978-2-88919-750-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Cell-mediated immunity to extracellular and intracellular microbes has been traditionally linked to CD4+ and CD8+ T cells that recognize pathogen-derived peptides in the context of major histocompatibility complex (MHC) class II and class I molecules, respectively. Recent progress in our understanding of early host defense mechanisms has brought ‘unconventional’, innate-like T cells into the spotlight. These are a heterogeneous population of non-MHC-restricted T cells that exhibit ‘memory-like’ properties and mount emergency responses to infection. They may directly detect and destroy infected cells, but are best known for their ability to regulate downstream effector cells including but not limited to conventional T cells. Innate-like T cells include among others CD1-restricted natural killer T (NKT) cells and MR1-restricted mucosa-associated invariant T (MAIT) cells. NKT cells recognize lipid antigens, and MAIT cells were recently demonstrated to respond to microbe-derived vitamin B metabolites. However, much remains to be learned about the antigen specificity range of these cells, their activation mode and their true potentials in immunotherapeutic applications. Like in many other areas of biology, uncertainties and controversies surrounding these cells and some of the experimental models, techniques and reagents employed to study them have brought about excitement and sometimes hot debates. This Special Topic was launched to provide updated reviews on protective and/or pathogenic roles of NKT and MAIT cells during infection. Leading experts discuss current controversies, pressing questions and the challenges that lie ahead for the advancement of this intriguing and rapidly evolving area of immunology. Unlike MHC, CD1 and MR1 display very limited polymorphism. Therefore, NKT and MAIT cells may be considered attractive targets for various diseases in diverse human populations. The potential benefits of NKT cell- and MAIT cell-based vaccination and treatment strategies in infectious diseases is an important subject that is also covered in this Topic.

Recent advances in γδ T cell biology: New ligands, new functions, and new translational perspectives

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197842 Year: Pages: 269 DOI: 10.3389/978-2-88919-784-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-04-07 11:22:02
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Gamma/delta (γδ) T-cells are a small subset of T-lymphocytes in the peripheral circulation but constitute a major T-cell population at other anatomical localizations such as the epithelial tissues. In contrast to conventional a/ß T-cells, the available number of germline genes coding for T-cell receptor (TCR) variable elements of γδ T-cells is very small. Moreover, there is a prefential localization of γδ T-cells expressing given Vgamma and Vdelta genes in certain tissues. In humans, γδ T-cells expressing the Vg9Vd2-encoded TCR account for anywhere between 50 and >95% of peripheral blood γδ T-cells, whereas cells expressing non-Vd2 genes dominate in mucosal tissues. In mice, there is an ordered appearance of γδ T-cell „waves“ during embryonic development, resulting in preferential localization of γδ T-cells expressing distinct VgammaVdelta genes in the skin, the reproductive organs, or gut epithelia. The major function of γδ T-cells resides in local immunosurveillance and immune defense against infection and malignancy. This is supported by the identification of ligands that are selectively recognized by the γδ TCR. As an example, human Vgamma9Vdelta2 T-cells recognize phosphorylated metabolites („phosphoantigens“) that are secreted by many pathogens but can also be overproduced by tumor cells, providing a basis for a role of these γδ T-cells in both anti-infective and anti-tumor immunity. Similarly, the recognition of endothelial protein C receptor by human non-Vdelta2 γδ T-cells has recently been identified to provide a link for the role for such γδ T-cells in immunity against epithelial tumor cells and cytomegalovirus-infected endothelial cells. In addition to „classical“ functions such as cytokine production and cytotoxicity, recent studies suggest that subsets of γδ T-cells can exert additional functions such as regulatory activity and – quite surpisingly – „professional“ antigen-presenting capacity. It is currently not well known how this tremendous extent of functional plasticity is regulated and what is the extent of γδ TCR ligand diversity. Due to their non-MHC-restricted recognition of unusual stress-associated ligands, γδ T-cells have raised great interest as to their potential translational application in cell-based immunotherapy. Topics of this Research Focus include: Molecular insights into the activation and differentiation requirements of γδ T-cells, role of pyrophosphates and butyrophilin molecules for the activation of human γδ T-cells, role of γδ T-cells in tumor immunity and in other infectious and non-infectious diseases, and many others. We are most grateful to all colleagues who agreed to write a manuscript. Thanks to their contributions, this E-book presents an up-to-date overview on many facets of the still exciting γδ T-cells.

Regulatory potential of post-translational modifications in bacteria

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196104 Year: Pages: 204 DOI: 10.3389/978-2-88919-610-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2016-08-16 10:34:25
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Post-translational modifications (PTMs) are widely employed by all living organisms to control the enzymatic activity, localization or stability of proteins on a much shorter time scale than the transcriptional control. In eukarya, global analyses consistently reveal that proteins are very extensively phosphorylated, acetylated and ubiquitylated. Glycosylation and methylation are also very common, and myriad other PTMs, most with a proven regulatory potential, are being discovered continuously. The emergent picture is that PTM sites on a single protein are not independent; modification of one residue often affects (positively or negatively) modification of other sites on the same protein. The best example of this complex behavior is the histone “bar-code” with very extensive cross-talk between phosphorylation, acetylation and methylation sites.Traditionally it was believed that large networks of PTMs exist only in complex eukaryal cells, which exploit them for coordination and fine-tuning of various cellular functions. PTMs have also been detected in bacteria, but the early examples focused on a few important regulatory events, based mainly on protein phosphorylation. The global importance (and abundance) of PTMs in bacterial physiology was systematically underestimated. In recent years, global studies have reported large datasets of phosphorylated, acetylated and glycosylated proteins in bacteria. Other modifications of bacterial proteins have been recently described: pupylation, methylation, sirtuin acetylation, lipidation, carboxylation and bacillithiolation. As the landscape of PTMs in bacterial cells is rapidly expanding, primarily due to advances of detection methods in mass spectrometry, our research field is adapting to comprehend the potential impact of these modifications on the cellular physiology. The field of protein phosphorylation, especially of the Ser/Thr/Tyr type, has been profoundly transformed. We have become aware that bacterial kinases phosphorylate many protein substrates and thus constitute regulatory nodes with potential for signal integration. They also engage in cross-talk and eukaryal-like mutual activation cascades. The regulatory potential of protein acetylation and glycosylation in bacteria is also rapidly emerging, and the cross-talk between acetylation and phosphorylation has been documented. This topic deals with the complexity of the PTM landscape in bacteria, and focus in particular on the physiological roles that PTMs play and methods to study them. The topic is associated to the 1st International Conference on Post-Translational Modifications in Bacteria (September 9-10, 2014, Göttingen, Germany).

Lutte contre le trachome en Afrique subsaharienne

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ISBN: 9782709917735 Year: DOI: 10.4000/books.irdeditions.5046 Language: French
Publisher: IRD Éditions
Subject: Social Sciences
Added to DOAB on : 2017-06-09 10:17:46
License: OpenEdition Licence for Books

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Le trachome, la maladie des « cils qui poussent à l’intérieur », est la deuxième cause de cécité dans le monde. Bien qu’elle soit susceptible d’être prévenue et traitée, elle frappe encore près de 80 millions de personnes, en particulier dans le sud du Sahara. Quelles sont les causes de cette maladie ? Comment y faire face ? Comment évaluer le succès des actions préventives ou curatives déjà entreprises ? Où en est la lutte contre cette infection et quelles sont les recommandations nécessaires à son éradication ? Cette expertise collégiale menée par l’IRD, réalisée par une quinzaine de chercheurs à la demande du ministère de la Santé du Mali et de l’Institut d’ophtalmologie tropicale d’Afrique (Mali), s’attache à décrire l’état actuel de la lutte contre cette conjonctivite cécitante d’origine infectieuse. En dressant le bilan des stratégies déjà à l’œuvre, notamment celle du programme CHANCE de l’OMS, cette expertise cherche à définir les conditions et les perspectives de cette maladie.

Phage Therapy: Past; Present and Future

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452514 Year: Pages: 392 DOI: 10.3389/978-2-88945-251-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2018-02-27 16:16:44
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Historically, the first observation of a transmissible lytic agent that is specifically active against a bacterium (Bacillus anthracis) was by a Russian microbiologist Nikolay Gamaleya in 1898. At that time, however, it was too early to make a connection to another discovery made by Dmitri Ivanovsky in 1892 and Martinus Beijerinck in 1898 on a non-bacterial pathogen infecting tobacco plants. Thus the viral world was discovered in two of the three domains of life, and our current understanding is that viruses represent the most abundant biological entities on the planet. The potential of bacteriophages for infection treatment have been recognized after the discoveries by Frederick Twort and Felix d’Hérelle in 1915 and 1917. Subsequent phage therapy developments, however, have been overshadowed by the remarkable success of antibiotics in infection control and treatment, and phage therapy research and development persisted mostly in the former Soviet Union countries, Russia and Georgia, as well as in France and Poland. The dramatic rise of antibiotic resistance and especially of multi-drug resistance among human and animal bacterial pathogens, however, challenged the position of antibiotics as a single most important pillar for infection control and treatment. Thus there is a renewed interest in phage therapy as a possible additive/alternative therapy, especially for the infections that resist routine antibiotic treatment. The basis for the revival of phage therapy is affected by a number of issues that need to be resolved before it can enter the arena, which is traditionally reserved for antibiotics. Probably the most important is the regulatory issue: How should phage therapy be regulated? Similarly to drugs? Then the co-evolving nature of phage-bacterial host relationship will be a major hurdle for the production of consistent phage formulae. Or should we resort to the phage products such as lysins and the corresponding engineered versions in order to have accurate and consistent delivery doses? We still have very limited knowledge about the pharmacodynamics of phage therapy. More data, obtained in animal models, are necessary to evaluate the phage therapy efficiency compared, for example, to antibiotics. Another aspect is the safety of phage therapy. How do phages interact with the immune system and to what costs, or benefits? What are the risks, in the course of phage therapy, of transduction of undesirable properties such as virulence or antibiotic resistance genes? How frequent is the development of bacterial host resistance during phage therapy? Understanding these and many other aspects of phage therapy, basic and applied, is the main subject of this Topic.

Plants; Stress & Proteins

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452675 Year: Pages: 323 DOI: 10.3389/978-2-88945-267-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany
Added to DOAB on : 2018-02-27 16:16:44
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Biotic and abiotic stress factors deliver a huge impact on plant life. Biotic stress factors such as damage through pathogens or herbivore attack, as well as abiotic stress factors like variation in temperature, rainfall and salinity, have placed the plant kingdom under constant challenges for survival. As a consequence, global agricultural and horticultural productivity has been disturbed to a large extent. Being sessile in nature, plants cannot escape from the stress, and instead adapt changes within their system to overcome the adverse conditions. These changes include physiological, developmental and biochemical alterations within the plant body which influences the genome, proteome and metabolome profiles of the plant. Since proteins are the ultimate players of cellular behavior, proteome level alterations during and recovery period of stress provide direct implications of plant responses towards stress factors. With current advancement of modern high-throughput technologies, much research has been carried out in this field. This e-book highlights the research and review articles that cover proteome level changes during the course or recovery period of various stress factors in plant life. Overall, the chapters in this e-book has provided a wealth of information on how plants deal with stress from a proteomics perspective.

Molecular Pathogenesis of Pneumococcus

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452781 Year: Pages: 110 DOI: 10.3389/978-2-88945-278-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Internal medicine
Added to DOAB on : 2018-02-27 16:16:44
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Streptococcus pneumoniae has been for decades the number one bacterial killer of children in the world. Although vaccination with pneumococcal vaccines [PCV7, PCV10, and PCV13 (children) or PPSV23 (adults)] has helped decrease the burden of pneumococcal disease (PD), mortality remains high. Therefore, pathogenesis studies are still key toward our understanding of PD and its control. The introduction of pneumococcal vaccines has also created a niche for vaccine-escape clones. Moreover, the rise of multi-drug resistant clones around the world has also posed a serious threat in recent years. The proposed special issue of Frontiers in Cellular and Infection Microbiology highlights many of the recent advances that have been made in pneumococcal pathogenesis, colonization and antibiotic resistance by groups in Latino America, Europe, and the USA.

NETosis 2: The Excitement Continues

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453795 Year: Pages: 362 DOI: 10.3389/978-2-88945-379-5 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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NETosis, a form of cell death that manifests by the release of decondensed chromatin to the extracellular space, provides valuable insights into mechanisms and consequences of cellular demise. Because extracellular chromatin can immobilize microbes, the extended nucleohistone network was called a neutrophil extracellular trap (NET), and the process of chromatin release was proposed to serve an innate immune defense function. Extracellular chromatin NETs were initially observed in studies of neutrophils and are most prominent in these types of granulocytes. Subsequent studies showed that other granulocytes and, in a limited way, other cells of the innate immune response may also release nuclear chromatin following certain kinds of stimulation. Variations of NETosis were noted with cells that remain temporarily motile after the release of chromatin. Numerous stimuli for NETosis were discovered, including bacterial breakdown products, inflammatory stimuli, particulate matter, certain crystals, immune complexes and activated thrombocytes. Fundamental explorations into the mechanisms of NETosis observed that neutrophil enzyme activity (PAD4, neutrophil elastase, proteinase 3 and myeloperoxidase) and signal transduction pathways contribute to the regulation of NETosis. Histones in NET chromatin become modified by peptidylarginine deiminase 4 (PAD4) and cleaved at specific sites by proteases, leading to extensive chromatin externalization. In addition, NETs serve for attachment of bactericidal enzymes including myeloperoxidase, leukocyte proteases, and the cathelicidin LL-37. NETs are decorated with proteases and may thus contribute to tissue destruction. However, the attachment of these enzymes to NET-associated supramolecular structures restricts systemic spread of the proteolytic activity. While the benefit of NETs in an infection appears obvious, NETs also participate as key protagonists in various pathologic states. Therefore, it is essential for NETs to be efficiently cleared; otherwise digestive enzymes may gain access to tissues where inflammation takes place. Persistent NET exposure at sites of inflammation may lead to a further complication: NET antigens may provoke acquired immune responses and, over time, could initiate autoimmune reactions, serve as antigen for nuclear autoantibodies and foster DNA immune complex-related inflammation. Neutrophil products and deiminated proteins comprise an important group of autoantigens in musculoskeletal disorders. Aberrant NET synthesis and/or clearance are often associated with inflammatory and autoimmune conditions. Recent evidence also implicates aberrant NET formation in the development of endothelial damage, atherosclerosis and thrombosis. Intravital microscopy provides evidence for conditions that induce NETosis in vivo. Furthermore, NETs can easily be detected in synovial fluid and tissue sections of patients with arthritis and gout. NETosis is thus of interest to researchers who investigate innate immune responses, host-pathogen interactions, chronic inflammatory disorders, cell and vascular biology, biochemistry, and autoimmunity. As we enter the second decade of research on NETosis, it is useful and timely to review the mechanisms and pathways of NET formation, their role in bacterial and fungal defense and their importance as inducers of autoimmune responses.

Immunobiotics: Interactions of Beneficial Microbes with the Immune System

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453825 Year: Pages: 309 DOI: 10.3389/978-2-88945-382-5 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology --- Science (General) --- Microbiology
Added to DOAB on : 2018-11-16 17:17:57
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The term “immunobiotics” has been proposed to define microbial strains able to beneficially regulate the mucosal immune system. Research in immunobiotics has significantly evolved as researchers employed cutting-edge technologies to investigate the complex interactions of these beneficial microorganisms with the immune system. During the last decade, our understanding of immunobiotics-host interaction was profoundly transformed by the discovery of microbial molecules and host receptors involved in the modulation of gut associated immune system, as well as the systemic and distant mucosal immune systems. In recent years, there has been a substantial increase in the number of reports describing the beneficial effects of immunobiotics in diseases such as intestinal and respiratory infections, allergy, inflammatory bowel disease, obesity, immunosuppression, and several other immune-mediated conditions. Evidence is also emerging of immunobiotics related molecules with immunomodulatory functions leading to the production of pharmabiotics, which may positively influence human or animal health. Therefore, research in immunobiotics continue to contribute not only to food but also medical and pharmaceutical fields. The compilation of research articles included in this ebook should help reader to have an overview of the recent advances in immunobiotics.

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