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Platelets as immune cells in physiology and immunopathology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197408 Year: Pages: 111 DOI: 10.3389/978-2-88919-740-8 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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Are platelets cells? (Not everyone agrees, since they are non-nucleate). And if platelets are cells - which all specialists consider at the time being - are they immune cells? The issue that platelets participate in immunity is no longer debated; however, the issue that they are key cells in immunity is challenged. It has even been proposed a couple of years ago that platelets can present antigen to T-lymphocytes by using their HLA class I molecules. No one has the same functional definition of platelets. The ‘Frontiers Research Topic’- coordinators’ own view is that platelets are primarily repairing cells, what they do in deploying tools of physiological inflammation. This function is better acknowledged as primary hemostasis, i.e. platelet adherence to injured or wounded vessels, followed by activation, aggregation, and constitution of the initial clot. Platelets would thus repair damaged vascular endothelium; so doing, as they patrol to detect damages, they sense danger along the vascular arborescence. As the latter is immense, platelets get close to tissues, which are not allowed to them under ‘physiological’ conditions but are readily accessible in pathology. Platelets are equipped with a variety of Pathogen Recognition Receptors such as TLRs; they have a complete signalosome, which is functional until the phosphorylation of NFkB; they have been proved to retro-transcribe RNA and synthesize de novo proteins; etc. Platelets participate to inflammation along the whole spectrum: from physiological (tissue repair, healing) to acute/severe inflammation (as can be seen in e.g. sepsis). In general, platelets engage complex interactions with most infectious pathogens. We propose there to cover those topics - from physiology to pathology, that put platelets within cells that not only take place in-, but also are key players of-, innate immunity. The relation of platelets with adaptive immunity is even more complex. Not everyone is convinced that platelets present antigens; however, platelets influence adaptive immunity since they have mutual interactions with Dendritic cells, Monocytes/Macrophages, and B-lymphocytes (the key players of antigen presentation); they also have mutual interactions with T-lymphocytes, though is issue is less clearly deciphered. We propose to also cover these topics - or to present the forum. There is another issue which is medically relevant - speaking of physiology/physiopathology-: this is fetal maternal incompatibility of platelet specific antigens (the HPA system) and the likely formation of maternal antibodies that often injure the newborn with risks of severe thrombocytopenia and intracranial hemorrhage. We propose an update on this issue as well. Last, platelets are very special because they can be directly therapeutic (by transfusion), even when being offered by a generous blood donor displaying given genetic and phenotypic parameters to a patient/recipient in need, who also display his/her own genetic and phenotypic parameters, which - for a large part - differ from the donor's ones. Besides immunization - via mechanisms probably close to the fetal maternal platelet incompatibility, but likely not similar -, transfusion has allowed the identification of the tremendous capacity of platelets to mediate inflammation: we propose to conclude the Topics with this item/forum.

Keywords

platelets --- Infection --- Inflammation --- immunity

Genomics and Effectomics of the Crop Killer Xanthomonas

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199020 Year: Pages: 158 DOI: 10.3389/978-2-88919-902-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany
Added to DOAB on : 2016-01-19 14:05:46
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Phytopathogenic bacteria of the Xanthomonas genus cause severe diseases on hundreds of host plants, including economically important crops, such as bean, cabbage, cassava, citrus, hemp, pepper, rice, sugarcane, tomato or wheat. Diseases occurring in nature comprise bacterial blight, canker, necrosis, rot, scald, spot, streak or wilt. Xanthomonas spp. are distributed worldwide and pathogenic and nonpathogenic strains are essentially found in association to plants. Some phytopathogenic strains are emergent or re-emergent and, consequently, dramatically impact agriculture, economy and food safety. During the last decades, massive efforts were undertaken to decipher Xanthomonas biology. So far, more than one hundred complete or draft genomes from diverse Xanthomonas species have been sequenced (http://www.xanthomonas.org), thus providing powerful tools to study genetic determinants triggering pathogenicity and adaptation to plant habitats. Xanthomonas spp. employ an arsenal of virulence factors to invade its host, including extracellular polysaccharides, plant cell wall-degrading enzymes, adhesins and secreted effectors. In most xanthomonads, type III secretion (T3S) system and secreted effectors (T3Es) are essential to bacterial pathogenicity through the inhibition of plant immunity or the induction of plant susceptibility (S) genes, as reported for Transcription Activation-Like (TAL) effectors. Yet, toxins can also be major virulence determinants in some xanthomonads while nonpathogenic Xanthomonas species do live in sympatry with plant without any T3S systems nor T3Es. In a context of ever increasing international commercial exchanges and modifications of the climate, monitoring and regulating pathogens spread is of crucial importance for food security. A deep knowledge of the genomic diversity of Xanthomonas spp. is required for scientists to properly identify strains, to help preventing future disease outbreaks and to achieve knowledge-informed sustainable disease resistance in crops. This Research Topic published in the ‘Plant Biotic Interactions’ section of Frontiers in Plant Science and Frontiers in Microbiology aims at illustrating several of the recent achievements of the Xanthomonas community. We collected twelve manuscripts dealing with comparative genomics or T3E repertoires, including five focusing on TAL effectors which we hope will contribute to advance research on plant pathogenic bacteria.

Innate immunity and neurodegenerative disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193103 Year: Pages: 87 DOI: 10.3389/978-2-88919-310-3 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Therapeutics --- Neurology --- Medicine (General) --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Inflammation of the brain in the context of neurodegenerative disorders is an area of intense debate and discussion, not least in terms of its pathogenic significance and the extent to which it drives disease processes and pathology. This inflammation can take several forms including innate responses recruiting microglia, humoral responses involving antibody, complement mediated processes and cellular T-cell activation, of which the role and extent of each may differ between diseases. Whilst some diseases have been more intensely linked to inflammation and long-term degeneration (e.g. MS), more traditional chronic neurodegenerative disorders have been thought of in terms of intrinsic neuronal pathology with a secondary innate response. However, it has been described that microglia activation is an early event of many degenerative disorders and evidence is accumulating that it may play a critical role in actually causing pathology and driving disease processes. If true, this would have major therapeutic implications, but what is the evidence that this is the case? The initial observations by Patrick McGeer’s group of post-mortem tissue from patients with Parkinson’s disease revealed the presence of activated brain microglia and has thus lead to the hypothesis that chronic inflammation could participate to neuronal degenerative processes. The significance of these original observations has only been recently revisited, and the development of more powerful tools to study the brain immune response has certainly contributed to this field of research. Chronic inflammation in the brain can take many forms but of particular interest has been the resident microglia and the role they play in this process. In this context, microglia have often been thought to become activated only after the disease has begun and then to contribute minimally to the degenerative process. Emerging new concepts challenge this view by proposing that microglial senescence, for example, may release the disease process and/or accelerate it. In addition, microglia, once activated, can adopt different phenotypes which can be both pro-inflammatory and pro-repair and may impact not only on the healthy adult neuronal population but on those new neurons derived from neurogenic niches of the adult brain. In this Research Topic, we attempt to explore this by first considering the innate immune responses in the brain and the methods by which they can be studied experimentally and in patients with various neurodegenerative disorders. This sets the scene for then discussing a range of different disorders including Alzheimer’s, Parkinson’s, Huntington’s disease and amyotrophic lateral sclerosis. These papers seek to discuss the evidence for an innate immune response and whether this is beneficial or detrimental, as well as its therapeutic implications.

HSPs - Ambiguous Mediators of Immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451524 Year: Pages: 92 DOI: 10.3389/978-2-88945-152-4 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-08-28 14:01:09
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Heat shock proteins (HSPs) were discovered as polypeptides induced by stress that can be found in all kingdoms of cellular organisms. Their functions were, a first enigmatic and these proteins were thus classified by molecular weight, as in—Hsp27, Hsp70, Hsp90, Hsp110. More recently, each of these size-classified molecules has attributed a role in protein folding, and they thus came to be known, as a class, as molecular chaperones. However, the they possess properties beyond chaperoning. Indeed, their discovery in the extracellular spaces suggested roles in regulation of the immune responses.

NLR-protein functions in immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196210 Year: Pages: 220 DOI: 10.3389/978-2-88919-621-0 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-08-16 10:34:25
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The Nod-like receptor (NLR) family of proteins are evolutionary conserved molecules that in plants and mammals have been implicated in innate immune sensing of microbes and infection-associated physiological changes, contributing to immune protection of the challenged host organism through the instruction of inflammatory responses, antimicrobial defense and adaptive immunity. Recent data however suggests that the biological roles of NLR go beyond the function of classical pattern recognition molecules (PRM) as they have been implicated in essential cellular processes including autophagy, apoptosis, modification of signal transduction and gene transcription as well as reproductive biology. In this research topic, we aim to provide a comprehensive state-of the art overview of the emerging functions of NLR in plant and mammalian immunity, cell biology and reproductive biology. Potential topics may include, but are not limited to the following areas: • Functions of NLRs as PRMs in infection • Cross-talk of NLRs with other PRMs • Signal transduction pathways of NLRs • New functions of NLRs other than pattern recognition • Structural aspects of NLR activation • Mechanisms of NLRs in cell biological processes • Aspects of NLRs in reproductive biology • Functions of NLRs in plant immune responses

Keywords

Adaptive Immunity --- Bacteria --- virus --- pathogens --- Sensing --- DAMP --- MAMP --- PAMP --- innate immunity --- LRR

Model organisms in inflammation and cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193707 Year: Pages: 83 DOI: 10.3389/978-2-88919-370-7 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Science (General)
Added to DOAB on : 2015-11-19 16:29:12
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A link between inflammation and cancer was initially made by Rudolf Virchow back in the 19th century. Nowadays many cancers are considered dependent on inflammatory responses to microbial and damaged-self stimuli and both arms of immunity, innate and adaptive, are playing a role in promoting cancer. Moreover, besides environmental factors, opportunistic pathogens contribute to inflammation and cancer. Nevertheless, microbial influence on chronic disease is sometimes difficult to discern, especially in the context of polymicrobial communities, such as those found in the digestive tract. In this light, model organisms provide important insights into immune and growth signals that promote cancer, and suggest therapies that will selectively target potentially harmful microbes or modulate host responses. A number of review and opinion articles in this series address novel aspects and paradigms of the interactions between the microbiota and the host in relation to inflammation and cancer.

Keywords

Drosophila --- human --- mouse --- innate immunity --- microbiota --- Hologenome --- diet --- aging

M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194995 Year: Pages: 280 DOI: 10.3389/978-2-88919-499-5 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2015-12-03 13:02:24
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Macrophages have unique and diverse functions necessary for survival. And, in humans (and other species), they are the most abundant leukocytes in tissues. The Innate functions of macrophages that are best known are their unusual ability to either "Kill" or "Repair". Since killing is a destructive process and repair is a constructive process, it was stupefying how one cell could exhibit these 2 polar – opposite functions. However, in the late 1980’s, it was shown that macrophages have a unique ability to enzymatically metabolize Arginine to Nitric Oxide (NO, a gaseous non – specific killer molecule) or to Ornithine (a precursor of polyamines and collagen for repair). The dual Arginine metabolic capacity of macrophages provided a functional explanation for their ability to kill or repair. Macrophages predominantly producing NO are called M1 and those producing Ornithine are called M2. M1 and M2 – dominant responses occur in lower vertebrates, and in T cell deficient vertebrates being directly driven by Damage and Pathogen Associated Molecular Patterns (DAMP and PAMP). Thus, M1 and M2 are Innate responses that protect the host without Adaptive Immunity. In turn, M1/M2 is supplanting previous models in which T cells were necessary to "activate" or "alternatively activate" macrophages (the Th1/Th2 paradigm). M1 and M2 macrophages were named such because of the additional key findings that these macrophages stimulate Th1 and Th2 – like responses, respectively. So, in addition to their unique ability to kill or repair, macrophages also govern Adaptive Immunity. All of the foregoing would be less important if M1 or M2 – dominant responses were not observed in disease. But, they are. The best example to date is the predominance of M2 macrophages in human tumors where they act like wound repair macrophages and actively promote growth. More generally, humans have become M2 – dominant because sanitation, antibiotics and vaccines have lessened M1 responses. And, M2 dominance seems the cause of ever - increasing allergies in developed countries. Obesity represents a new and different circumstance. Surfeit energy (e.g., lipoproteins) causes monocytes to become M1 dominant in the vessel walls causing plaques. Because M1 or M2 dominant responses are clearly causative in many modern diseases, there is great potential in developing the means to selectively stimulate (or inhibit) either M1 or M2 responses to kill or repair, or to stimulate Th1 or Th2 responses, depending on the circumstance. The contributions here are meant to describe diseases of M1 or M2 dominance, and promising new methodologies to modulate the fungible metabolic machinery of macrophages for better health.

Keywords

macrophage --- innate immunity --- M1 --- M2 --- wound --- Cancer --- Infection --- Atherosclerosis

Pathophysiology and epidemiology of virus-induced asthma

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194100 Year: Pages: 99 DOI: 10.3389/978-2-88919-410-0 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Microbiology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Virus-caused asthma, we now call a phenotype of asthma. Regardless of the significance and popularity of this disease, the etiology of the virus-induced asthma have not well understood. In addition, a few effective vaccines have been applied to prevent respiratory virus infection. To solve the issues, it is essential to clarify and delineate both aspects of the virus and host defense systems including acute/chronic inflammation and airway tissue remodeling. To deeply review and discuss pathophysiology and epidemiology of virus-induced asthma, this topics includes new findings of the host immunity, pathology, epidemiology, and virology of asthma/chronic obstructive pulmonary disease (COPD). We believe that these works are well summarized and informative to glimpse the field of virus- associated asthma and COPD, and may help understanding the basic and clinical aspects of the diseases.

Influenza Virus Vaccines and Immunotherapies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198115 Year: Pages: 185 DOI: 10.3389/978-2-88919-811-5 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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Influenza virus infections lead to thousands of deaths worldwide annually and billions of dollars economic burden. Despite continuing advances in our understanding of the immune evasion mechanism, the disease remains one of the foremost threat for human being. Traditional vaccines (attenuated and inactivated) mainly provide protection by inducing virus neutralizing antibodies, targeting ever changing surface antigens: Haemagultinin (HA) and Neuraminidase (NA). Due to genetic shift and immune selection pressure, prevalence of circulating influenza virus subtypes changes every year. Therefore, mismatch between circulating strain and vaccine strain can critically affect the success rate of these conventional flu vaccines, and requires continuous monitoring of circulating influenza virus subtypes and change in the vaccine formulations accordingly. The collective limitations of existing flu vaccines urgently call for the development of a novel universal vaccines that might provide the required protective immunity to a range of influenza virus subtypes. New approaches are being investigated mainly targeting conserved regions of flu proteins. Some of these approaches include universally conserved epitopes of HA, nucleoprotein (NP), capsid protein (M1) and ion channel protein (M2) that induced strong immune responses in animal models. Some attention and progress appears to be focused on vaccines based on the M2 ectodomain (M2e) employing a variety of constructs, adjuvants and delivery systems, including M2e-hepatitis B core antigen, flagellin constructs, and virus-like particles (VLP). Animal studies with these M2e candidate vaccines demonstrated that these vaccine candidates can prevent severe illness and death but not infection, which may pose difficulties in both the evaluation of clinical efficacy and approval by the regulatory authorities. VLP vaccines appear to be promising, but still are mostly limited to animal studies. The discovery and development of new and improved vaccines have been greatly facilitated by the application of new technologies. The use of nucleic acid-based vaccines, to combine the benefits of in-situ expression of antigens with the safety of inactivated and subunit vaccines, has been a key advancement. Upon their discovery more than 20 years ago, nucleic acid vaccines promised to be a safe and effective mean to mimic immunization with a live organism vaccine, particularly for induction of T cell immunity. In addition, the manufacturing of nucleic acid-based vaccines offered the potential to be relatively simple, inexpensive and generic. Reverse Vaccinology and in-silico designing of vaccines are very innovative approaches and being considered as future of vaccines. Furthermore, various immuno-therapeutic agents also being developed to treat and minimize immuno-pathological damage in patients suffering from life threatening complications. For the treatment of such pathological conditions, various novel approaches such as administration of immune suppressive cytokines, blocking co-stimulatory signals or activating co-inhibitory signal of T cell activation, are being tested both in lab and clinics. The Research Topic on influenza virus vaccine and therapeutics will give an insight in to the current status and future scope of these new innovative approaches and technologies. Moreover, these new methods will also serve as a reference tool for the development of future vaccines against several other pathogens.

History of Chemoattractant Research

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197019 Year: Pages: 61 DOI: 10.3389/978-2-88919-701-9 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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In the Research Topic "History of Chemoattractant Research" we will portray some of the key discoveries that helped to transform cell migration research into a global playing field within immunology (and beyond). Early progress had a profound effect on both, academia and industry. Today, numerous academic laboratories are fully engaged in compiling a detailed road map describing the highly complex network of immune and tissue cells that respond to chemoattractants. Industrial research, on the other hand, centers on drugs that interfere with immune cell traffic in inflammatory diseases and cancer. The following series of “short stories” provide personal accounts on key discoveries. The individual molecular discoveries enabled numerous research laboratories worldwide to unravel their significance in steady-state or pathological immune processes. Although ground-breaking in their own right, it is therefore worth emphasizing that rapid progress in chemoattractant research was made possible by many other laboratories who were not directly involved in the original discovery process. Therefore, the authors of this mini-series are discussing their findings in the context of time, place and subsequent progress enabled by their discoveries. It is hoped that a wide readership will find these accounts entertaining as well as educational although those who wish to gain a more detailed knowledge are referred to the many outstanding reviews on chemokines and other chemoattractants.

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