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The Mononuclear Phagocyte System (MPS) of vertebrates is composed of monocytes, macrophages and dendritic cells. Together, they form part of the first line of immune defense against a variety of pathogens (bacteria, fungi, parasites and viruses), and thus play an important role in maintaining organism homeostasis. The mode of transmission, type of replication and mechanism of disease-causing differ significantly for each pathogen, eliciting a unique immune response in the host. Within this context, the MPS acts as both the sentinel and tailor of the immune system. As sentinels, MPS cells are found in blood and within tissues throughout the body to patrol against pathogenic insult. The strategy to detect 'microbial non-self' relies on MPS to recognize conserved microbial products known as 'pathogen-associated molecular pattern' (PAMPs). PAMPs recognition represents a checkpoint in the response to pathogens and relies on conserved 'pattern recognition receptors' (PRRs). Upon PRR engagement, MPS mount a cell-autonomous attack that includes the internalization and compartmentalization of intracellular pathogens into toxic compartments that promote destruction. In parallel, MPS cells launch an inflammatory response composed of a cellular arm and soluble factors to control extracellular pathogens. In cases when innate immunity fails to eliminate the invading microbe, MPS serves as a tailor to generate adaptive immunity for pathogen eradication and generation of "memory" cells, thus ensuring enhanced protection against re-infection. Indeed, MPS cell functions comprise the capture, process, migration and delivery of antigenic information to lymphoid organs, where type-1 immunity is tailored against intracellular microbes and type-2 immunity against extracellular pathogens. However, this potent adaptive immunity is also a double-edge sword that can cause aberrant inflammatory disorders, like autoimmunity or chronic inflammation. For this reason, MPS also tailors tolerance immunity against unwanted inflammation. Successful clearance of the microbe results in its destruction and proper collection of debris, resolution of inflammation and tissue healing for which MPS is essential. Reciprocally, as part of the evolutionary process taking place in all organisms, microbes evolved strategies to circumvent the actions bestowed by MPS cells. Multiple pathogens modulate the differentiation, maturation and activation programs of the MPS, as an efficient strategy to avoid a dedicated immune response. Among the most common evasion strategies are the subversion of phagocytosis, inhibition of PRR-mediated immunity, resistance to intracellular killing by reactive oxygen and nitrogen species, restriction of phagosome maturation, modulation of cellular metabolism and nutrient acquisition, regulation of cell death and autophagy, and modulation of pro-inflammatory responses and hijacking of tolerance mechanisms, among others. The tenet of this eBook is that a better understanding of MPS in infection will yield insights for development of therapeutics to enhance antimicrobial processes or dampen detrimental inflammation for the host's benefit. We believe that contributions to this topic will serve as a platform for discussion and debate about relevant issues and themes in this field. Our aim is to bring expert junior and senior scientists to address recent progress, highlight critical knowledge gaps, foment scientific exchange, and establish conceptual frameworks for future MPS investigation in the context of infectious disease.
The mononuclear phagocyte system (MPS) comprises dendritic cells (DCs), monocytes and macrophages (MØs) that together play crucial roles in tissue immunity and homeostasis, but also contribute to a broad spectrum of pathologies. They are thus attractive therapeutic targets for immune therapy. However, the distinction between DCs, monocytes and MØ subpopulations has been a matter of controversy and the current nomenclature has been a confounding factor. DCs are remarkably heterogeneous and consist of multiple subsets traditionally defined by their expression of various surface markers. While markers are important to define various populations of the MPS, they do not specifically define the intrinsic nature of a cell population and do not always segregate a bona fide cell type of relative homogeneity. Markers are redundant, or simply define distinct activation states within one subset rather than independent subpopulations. One example are the steady-state CD11b+ DCs which are often not distinguished from monocytes, monocyte-derived cells, and macrophages due to their overlapping phenotype. Lastly, monocyte fate during inflammation results in cells bearing the phenotypic and functional features of both DCs and MØs significantly adding to the confusion. In fact, depending on the context of the study and the focus of the laboratory, a monocyte-derived cell will be either be called "monocyte-derived DCs" or "macrophages". Because the names we give to cells are often associated with a functional connotation, this is much more than simple semantics. The "name" we give to a population fundamentally changes the perception of its biology and can impact on research design and interpretation. Recent evidence in the ontogeny and transcriptional regulation of DCs and MØs, combined with the identification of DC- and MØ-specific markers has dramatically changed our understanding of their interrelationship in the steady state and inflammation. In steady state, DCs are constantly replaced by circulating blood precursors that arise from committed progenitors in the bone marrow. Similarly, some MØ populations are also constantly replaced by circulating blood monocytes. However, others tissue MØs are derived from embryonic precursors, are seeded before birth and maintain themselves in adults by self-renewal. In inflammation, such differentiation pathways are fundamentally changed and unique monocyte-derived inflammatory cells are generated. Current DC, monocyte and MØ nomenclature does not take into account these new developments and as a consequence is quite confusing. We believe that the field is in need of a fresh view on this topic as well as an upfront debate on DC and MØ nomenclature. Our aim is to bring expert junior and senior scientists to revisit this topic in light of these recent developments. This Research Topic will cover all aspects of DC, monocyte and MØ biology including development, transcriptional regulation, functional specializations, in lymphoid and non-lymphoid tissues, and in both human and mouse models. Given the central position of DCs, monocytes and MØs in tissue homeostasis, immunity and disease, this topic should be of interest to a large spectrum of the biomedical community.
Immunobiology of the Macrophage presents an account of the state of knowledge of the immunobiology of the macrophage. The book's contributors—immunologists of diverse scientific and geographic backgrounds—have been encouraged to give personal accounts of developments in their special fields of interest as well as critical surveys of the backgrounds leading to these developments. The book begins with a study on the functions of macrophages in the initiation and regulation of antibody responses in vitro. This is followed by separate chapters on topics such as the role of macrophages in making antigen more immunogenic and less tolerogenic; functional distinctions between macrophages at different sites; and the role of the macrophage in antigen recognition by T lymphocytes. Subsequent chapters examine interactions between macrophages and lymphocytes in the production of interferon and other mediators of cellular immunity; macrophage cell lines and their uses in immunobiology; and cytotoxic macrophages in allograft rejection.
The structure, functions, and interactions of myeloid cells have long been the focus of research and therapeutics development. Yet, much more remains to be discovered about the complex web of relationships that makes up the immune systems of animals. Scientists today are applying genome-wide analyses, single-cell methods, gene editing, and modern imaging techniques to reveal new subclasses of differentiated myeloid cells, new receptors and cytokines, and important interactions among immune cells. In Myeloid Cells in Health and Disease: A Synthesis, Editor Siamon Gordon has assembled an international team of esteemed scientists to provide their perspectives of myeloid cells during innate and adaptive immunity. The book begins by presenting the foundational research of Paul Ehrlich, Elie Metchnikoff, and Donald Metcalf. The following chapters discuss evolution and the life cycles of myeloid cells; specific types of differentiated myeloid cells, including macrophage differentiation; and antigen processing and presentation. The rest of the book is organized by broad topics in immunology, including the recruitment of myeloid and other immune cells following microbial infection the role of myeloid cells in the inflammation process and the repair of damaged tissue the vast arsenal of myeloid cell secretory molecules, including metalloproteinases, tumor necrosis factor, histamine, and perforin receptors and downstream signaling pathways that are activated following ligand-receptor binding roles of myeloid cells during microbial and parasite infections contributions of myeloid cells in atherosclerosis myeloid-derived suppressor cells in tumor development and cancer Myeloid Cells in Health and Disease: A Synthesis will benefit graduate students and researchers in immunology, hematology, microbial pathogenesis, infectious disease, pathology, and pharmacology. Established scientists and physicians in these and related fields will enjoy the book's rich history of myeloid cell research and suggestions for future research directions and potential therapies.
“Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.
The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Myelomonocytes are the multipotent cells in the stage of blood cell differentiation, which mainly comprise blood monocytes, tissue macrophages and subset of dendritic cells. Actually, their position and ability of judgement of the health of tissue or organ environment are the key initiators of tissue-specific immune response in a local and global fashion. Interestingly, the morpho-functional aspects of this group of cells vary to a wide range with their positional diversity. Their ability to communicate or represent the tissue microenvironment to the peripheral immune system and efficiency to engage the system to effector activation hold the key for a successful immune endeavour. The present volume shows some glimpses of such an extensive area of current immunology research.
The International Life Sciences Institute (ILSI) was estab lished in 1978 to stimulate and support scientific research and educational programs related to nutrition, toxicology, and food safety, and to encourage cooperation in these programs among scientists in universities, industry, and government agencies to assist in the resolution of health and safety issues. To supplement and enhance these efforts, ILSI has made a major commitment to supporting programs to harmon ize toxicologic testing, to advance a more uniform inter pretation of bioassay results worldwide, to promote a common understanding of lesion classifications, and to encourage wide discussion of these topics among scien tists. The Monographs on the Pathology of Laboratory Ani mals are designed to facilitate communication among those involved in the safety testing of foods, drugs, and chemicals. The complete set will cover all organ systems and is intended for use by pathologists, toxicologists, and others concerned with evaluating toxicity and carcinogen icity studies. The international nature of the project - as reflected in the composition of the editorial board and the diversity of the authors and editors - strengthens our ex pectations that understanding and cooperation will be im proved worldwide through the series. Alex Malaspina President International Life Sciences Institute Preface This book, on the hemopoietic system, is the eighth volume of a set prepared under the sponsorship of the International Life Sciences In stitute (ILSI).