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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

The unfolded protein response in virus infections

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193974 Year: Pages: 129 DOI: 10.3389/978-2-88919-397-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology --- Botany
Added to DOAB on : 2015-12-03 13:02:24
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Unfolded protein response (UPR) is a cellular adaptive response for restoring endoplasmic reticulum (ER) homeostasis in response to ER stress. Perturbation of the UPR and failure to restore ER homeostasis inevitably leads to diseases. It has now become evident that perturbation of the UPR is the cause of many important human diseases such as neurodegenerative diseases, cystic fibrosis, diabetes and cancer. It has recently emerged that virus infections can trigger the UPR but the relationship between virus infections and host UPR is intriguing. On one hand, UPR is harmful to the virus and virus has developed means to subvert the UPR. On the other hand, virus exploits the host UPR to assist in its own infection, gene expression, establishment of persistence, reactivation from latency and to evade the immune response. When this delicate balance of virus-host UPR interaction is broken down, it may cause diseases. This is particularly challenging for viruses that establish a chronic infection to maintain this balance. Each virus interacts with the host UPR in a different way to suit their life style and how the virus interacts with the host UPR can define the characteristic of a particular virus infection. Understanding how a particular virus interacts with the host UPR may pave the way to the design of a new class of anti-viral that targets this particular pathway to skew the response towards anti-virus. This knowledge can also be translated into the clinics to help re-design oncolytic virotherapy and gene therapy. In this research topic we aimed to compile a collection of focused review articles, original research articles, commentary, opinion, hypothesis and methods to highlight the current advances in this burgeoning area of research, in an attempt to provide an in-depth understanding of how viruses interact with the host UPR, which may be beneficial to the future combat of viral and human diseases.

Obesity-induced inflammation and insulin resistance

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194285 Year: Pages: 120 DOI: 10.3389/978-2-88919-428-5 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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Immune response and metabolic regulation are highly integrated and this interface maintains a central homeostatic system, dysfunction of which can cause obesity-associated metabolic disorder such as type 2 diabetes, fatty liver disease and cardiovascular disease. Insulin resistance is an underlying basis for the pathogenesis of these metabolic diseases. Overnutrition or obesity activates the innate immune system with subsequent recruitment of immune cells such as macrophages and T cells, which contributes to the development of insulin resistance. In particular, a significant advance in our understanding of obesity-associated inflammation and insulin resistance has been recognition of the critical role of adipose tissue macrophages (ATMs). ATMs are a prominent source of proinflammatory cytokines, such as TNF-a and IL-6, that can block insulin action in adipose tissue, skeletal muscle, and liver autocrine/paracrine signaling and cause systemic insulin resistance via endocrine signaling, providing a potential link between inflammation and insulin resistance. All articles in this topic highlight the interconnection between obesity, inflammation, and insulin resistance in all its diversity to the mechanisms of obesity-induced inflammation and role of immune system in the pathogenesis of insulin resistance and diabetes.

Reversible Ubiquitylation in Plant Biology

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194414 Year: Pages: 115 DOI: 10.3389/978-2-88919-441-4 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Reversible ubiquitylation plays an important regulatory role in almost all aspects of cellular and organismal processes in plants. Its pervasive regulatory role in plant biology is primarily due to the involvement of a large set of ubiquitin system constituents (encoded by approximately 6% Arabidopsis genome), the huge number of important cellular proteins targeted as substrates, and various drastic effects on the modified proteins. The major components of the ubiquitin system include a large set of enzymes and proteins involved in ubiquitin conjugation (E1s, E2s, and E3s) and deconjugation (deubiquitinases of different classes) and post ubiquitin conjugation components such as ubiquitin receptors, endocytic machineries, and 26S proteasome. The established substrates include transcriptional activators and repressors, signaling components, key metabolic enzymes, and critical mechanistic components of major cellular processes and regulatory mechanisms. Post-translational modification of proteins by reversible ubiquitylation could drastically affects the modified proteins by proteolytic processing and turnover, altering catalytic activity, subcellular targeting, and protein-protein interaction. Continued efforts are being carried out to identify novel substrates critical for various cellular and organismal processes, to determine effects of reversible ubiquitylation on the modified substrates, to determine signaling determinants triggering reversible ubiquitylation of specific substrates, to illustrate individual components of the ubiquitin system for their in vivo functions and involved mechanistic roles, and to determine mechanistic roles of modification acting on critical components of major cellular processes and regulatory mechanisms. The aim of this special topic is to serve as a platform to report most recent advances on those above listed current research endeavors. We welcome article types including original research, review, mini review, method, and perspective/opinion/hypothesis.

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

Interaction of Nanomaterials with the Immune System: Role in Nanosafety and Nanomedicinenanomedicine

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453870 Year: Pages: 177 DOI: 10.3389/978-2-88945-387-0 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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The immune system has the double role of maintaining tissue integrity and homeostasis and of protecting the organism from possible dangers, from invading pathogens to environmentally-borne dangerous chemicals. New chemicals recognisable by the immune system are engineered nanomaterials/ nanoparticles, new agents in our environment that are becoming common due to their presence in many products, from constructions and building material (e.g., solar cells, pigments and paints, tiles and masonry materials) to daily products (e.g., food packaging, cosmetics, and cigarettes). Human beings can be accidentally exposed to engineered nanomaterials when these are released from products containing them or during production in workplaces. Furthermore, intentional exposure occurs in medicine, as engineered nanoparticles are used as tools for improving delivery of drugs and vaccines, vaccine adjuvants and contrast agents in therapeutic, preventive and diagnostic strategies. Nanoparticles that come in contact with the immune system after unintentional exposure need to be eliminated from the organism as they represent a potential threat. In this case, however, due to their peculiar characteristics of size, shape, surface charge and persistence, nanoparticles may elicit undesirable reactions and have detrimental effects on the immune system, such as cytotoxicity, inflammation, anaphylaxis, immunosuppression. Conversely, nanomedicines need to escape immune recognition/elimination and must persist in the organism long enough for reaching their target and exerting their beneficial effects. Immune cells and molecules at the body surface (airway and digestive mucosae, skin) are the first that come in contact with nanomaterials upon accidental exposure, while immune effectors in blood are those that more easily come in contact with nanomedical products. Thus, evaluating the interaction of the immune system with nanoparticles/nanomaterials is a topic of key importance both in nanotoxicology and in nanomedicine. Immuno-nanosafety studies consider both accidental exposure to nanoparticles, which may occur by skin contact, ingestion or inhalation (at doses and with a frequency that are not known), and medical exposure, which takes place with a defined administration schedule (route, dose, frequency). Many studies focus on the interaction between the immune system and nanoparticles that, for medical purposes, have been specifically modified to stimulate immunity or to avoid immune recognition, as in the case of vaccine carriers/adjuvants or drug delivery systems, respectively. The aims of this Research Topic is to provide an overview of recent strategies: 1.for assessing the immunosafety of engineered nanomaterials/nanoparticles, in particular in terms of activation of inflammatory responses, such as complement activation and allergic reactions, based on the nanomaterial intrinsic characteristics and on the possible carry-over of bioactive contaminants such as LPS. Production of new nanoparticles taking into account their effects on immune responses, in order to avoid undesirable effects on one hand, and to design particles with desirable effects for medical applications on the other hand; 2.for designing more effective nanomedicines by either avoiding or exploiting their interaction with the immune systems, with particular focus on cancer diagnosis and therapy, and vaccination. This collection of articles gives a comprehensive view of the state-of-the-art of the interaction of nanoparticles with the immune system from the two perspectives of safety and medical use, and aims at providing immunologists with the relevant knowledge for designing improved strategies for immunologically safe nanomaterial applications.

Natural Antibodies in Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454051 Year: Pages: 180 DOI: 10.3389/978-2-88945-405-1 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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Natural antibodies (NAbs) are found in normal individuals in the absence of exogenous antigenic stimulation. Natural antibodies rapidly recognize and protect against pathogens that have not been previously encountered. NAbs also cross-react with several self-antigens, which, besides their role as a first line of defense against pathogens, affords them the ability to perform important housekeeping functions in healthy organisms. Such housekeeping functions include the clearance of oxidized damaged structures and/or apoptotic cells, which prevents the induction of pro-inflammatory effects. In addition, NAbs play a role in preventing the expansion of specific auto-reactive clones, thereby behaving as regulatory elements in acute or chronic inflammation. To maintain the non-pathogenic balance between the dual pathogen/self-antigen cross-reactivities of NAbs, a strict regulation in NAb secretion and function is necessary to avoid autoimmune disease. Actually, some of the NAbs related auto-reactivities, such as anti-DNA and anti-MOG, have been associated with autoimmunity. Furthermore, NAbs have been shown to bind to ‘neo-self’ carbohydrate antigens on glycolipids and glycoproteins found on malignant but not normal cells, which suggests NAbs may take part in tumor immunosurveillance.Many aspects regarding NAbs have yet to be studied in more detail: the reactivity and function of NAbs in health and disease, the behavior of the NAb repertoire with increasing age, the regulation of natural antibody production and auto-reactivity, the ways to specifically activate NAbs producing cells with desired specificities, the characteristics of human NAbs, among others. This special topics eBook consists of a number of articles exploring the cells that produce NAbs as well as the characteristics, function, specificity, and/or the role of natural antibodies in health and disease.

Cell Signaling in Host-Pathogen Interactions: The Host Point of View

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454556 Year: Pages: 414 DOI: 10.3389/978-2-88945-455-6 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 ability of pathogens, such as parasites, bacteria, fungi and viruses to invade, persist and adapt in both invertebrate and vertebrate hosts is multifactorial and depends on both pathogen and host fitness. Communication between a pathogen and its host relies on a wide and dynamic array of molecular interactions. Through this constant communication most pathogens evolved to be relatively benign, whereas killing of its host by a pathogen represents a failure to adapt. Pathogens are lethal to their host when their interaction has not been long enough for adaptation. Evolution has selected conserved immune receptors that recognize signature patterns of pathogens as non-self elements and initiate host innate responses aimed at eradicating infection. Conversely, pathogens evolved mechanisms to evade immune recognition and subvert cytokine secretion in order to survive, replicate and cause disease. The cell signaling machinery is a critical component of the immune system that relays information from the receptors to the nucleus where transcription of key immune genes is activated. Host cells have developed signal transduction systems to maintain homeostasis with pathogens. Most cellular processes and cell signaling pathways are tightly regulated by protein phosphorylation in which protein kinases are key protagonists. Pathogens have developed multiple mechanisms to subvert important signal transduction pathways such as the mitogen activated protein kinase (MAPK) and the nuclear factor kB (NF-kB) pathways. Pathogens also secrete effectors that manipulate actin cytoskeleton and its regulators, hijack cell cycle machinery and alter vesicular trafficking. This research topic focuses on the cellular signaling mechanisms that are essential for host immunity and their subversion by pathogens.

Lyme Disease: Recent Advances and Perspectives

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195572 Year: Pages: 114 DOI: 10.3389/978-2-88919-557-2 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Internal medicine
Added to DOAB on : 2016-01-19 14:05:46
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The interplay between host and pathogen is a complex co-evolutionary battle of surveillance and evasion. The pathogen continuously develops mechanisms to subvert the immune response in order to establish infection while the immune system responds with novel mechanisms of detection. Because the majority of Lyme disease pathology is due to an over-exuberant immune response, much research in Borrelia burgdorferi pathogenesis has been devoted to understanding the mammalian host response to the bacterium. Immunological studies continue to be an active area of research employing emerging techniques, such as intra-vital imaging. These studies have furthered our understanding of inflammatory processes during long-term infection and provided some surprising insights, such as the continued presence of bacterial products after clearance. The field of Lyme disease has long debated the etiology of long-term inflammation and recent studies in the murine host have shed light on relevant cell types and inflammatory mediators that participate in the pathology of Lyme arthritis. Live imaging and bioluminescent studies have allowed for a novel view of the bacterial life cycle, including the tick mid-gut, tick-to-mammal transmission and dissemination throughout a mouse. A number of tick and bacterial proteins have been shown to participate in the completion of the enzootic cycle. Novel mechanisms of gene regulation are continuously being identified. However, B. burgdorferi lacks many traditional virulence factors, such as toxins or specialized secretion systems. Many genes in the B. burgdorferi genome have no known homolog in other bacteria. Therefore, studies focusing on host-pathogen interactions have therefore been limited by an incomplete understanding of the repertoire of bacterial virulence factors. Questions such as how the pathogen causes disease, colonizes the tick and evades host immune-surveillance have been difficult to address. Genetic studies involving single gene deletions have identified a number of important bacterial proteins, but a large-scale genomics approach to identify virulence factors has not been attempted until recently. The generation of a site-directed mutagenesis library is an important step towards a detailed analysis of the B. burgdorferi genome and pathogenome. Using this library, high-throughput genomic studies, utilizing techniques such as massively parallel sequencing have been promising and could be used to identify novel virulence determinants of disease in the mammalian host or persistence in the tick vector. Continued research on this unique pathogen and its specific interaction with host and vector may have far reaching consequences and provide insights for diverse disciplines including ecology, infectious disease, and immunology. Here, several reviews will discuss the most recent advances and future studies to be undertaken in the field of B. burgdorferi biology.

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