Macrophages In Inflammation And Its Resolution

Macrophages were initially identified as a key element in the innate host response to infection and injury due to their phagocytic clearance and elimination of pathogenic and non-pathogenic entities. However, as macrophage research advanced it became clear that not only are these cells amenable to the acquisition of multiple plastic phenotypes during inflammatory responses to different pathogens, they also play a paramount role in the termination of inflammation and acquired immune responses. In addition, macrophages profoundly affect host physiology when they migrate to distant sites and differentiate to specialized cells, like foam cells, osteoclasts, adipose tissue- and tumor -associated macrophages and other macrophage-derived cell types. These processes are affected by the inflammation-resolution axis and can result in health threats, such as atherosclerosis, bone loss, obesity, fibrosis and cancer. This Research Topic issue will cover a wide range of topics in macrophage biology: 1. Macrophages in immune responses to pathogens 2. Macrophages in the termination of acute and acquired immunity. 3. The role of macrophages and their descendents in inflammation-associated pathologies. 4. Macrophage polarization and differentiation. Particular focus will be given to the modulation of macrophage phenotype and function following their encounter with apoptotic cells and the signaling cascades that govern these changes.

This book provides readers with an up-to-date and comprehensive view on the resolution of inflammation and on new developments in this area, including pro-resolution mediators, apoptosis, macrophage clearance of apoptotic cells, possible novel drug developments.

Macrophages are a key component of the innate immune system and play an integral role in host defense and homeostasis. On one hand, these cells contribute to host defence by triggering inflammation, displaying microbicidal/tumoricidal properties, regulating the activation of adaptive immunity and promoting resolution of inflammation. On the other hand, they contribute to essential trophic functions such as neural patterning, bone morphogenesis and ductal branching in mammary glands. Thus, macrophages are extremely versatile cells that can respond efficiently to tissue micro environmental cues by polarizing to distinct phenotypes, depending on the functions they need to perform. Indeed, functional diversity and plasticity are hallmarks of these cells. Macrophages may also play a detrimental role. An overwhelming body of literature has indicated their crucial role in pathogenesis. The list includes sepsis, cancer, metabolic syndrome, immunodeficiency, auto-immune disease-virtually impacting every major pathology that we know. These observations have suggested macrophages and their related molecules as potential targets in therapeutic applications. Available evidence proclaims macrophages as a key player in homeostasis, host defense and disease. Crucial developments in the past few years call for a re-evaluation and update of our understanding of macrophages. The present book is an endeavour that attempts provide state-of-the art knowledge of these cells in health and disease.

Offering a broad appeal to microbiologists, immunologists, and infectious disease specialists, this four volume encyclopedia covers all autoimmune, tropical, and infectious diseases. Emphasis will also be placed on genetics, physiology, metabolism, pathogenesis and applied microbiology. Under the leadership of some of the most world renowned names in the field, the encyclopedia will bring together an outstanding collection of contributions by top scientists in a variety of fields. Volumes 1-3: Diseases will be divided by the 11 main sections of the body, namely Integumentary, Skeletal, Respiratory, Digestive, Urinary, and Reproductive. For some of the autoimmune disease, more then one system will be involved but the delineation serves to broadly break down the diseases into systems. Volume 4 will cover the vaccines for said diseases and future prospects will be offered by leaders in industry and academia. Volume 4 will also be broken down into all the body systems, as in the other two volumes. For each vaccine, for each disease, and in each system the following will be included: • A list of the vaccines currently available along with a list of the companies that manufacture them • Molecular Immunology of the Vaccine • Type of Immunity involved in protection • Mode of Vaccination for each vaccine; repeated boosters and length of immunological memory • Commercial production of vaccines • Storage of vaccines • Standardization and Control of Vaccines • WHO programs and World-Wide Disease Eradication Programs based upon Vaccines.

It is by now widely recognized that atherosclerosis - with its burden of consequences in cerebro- and cardiovascular diseases - is just a chronic inflammatory process of the arterial wall. A very peculiar, complex and as yet still poorly understood process, upon which hundreds of scientists from several different fields are continuously concentrating their investigative efforts in search of possible leads to therapeutic approaches. Initiation of the disease is given by deposition of lipid in the intimal layers, resulting in endothelial activation and infiltration of blood-derived mononuclear cells. These mature into macrophages, become activated, express scavenger receptors such as SR-A and CD36 and ingest the oxidized lipoprotein accumulating in the lesion. Macrophages thus represent an obvious target for intervention, as they play a crucial role in the progression of the atherosclerotic inflammation. Studies have shown that hypercholesterolaemia can increase monocyte mobilisation from bone marrow into the circulation, and several chemokines and their receptors are involved in the recruitment of blood borne monocytes into the arterial wall. Monocyte-derived macrophages are capable of sustaining their local proliferation, but resident macrophages possibly also participate in progression of the disease. Remarkably, smooth muscle cells can acquire macrophage-like features during atherogenesis, including the ability to uptake lipid, thus becoming a significant proportion of the CD68+ so called 'foam cells'. Lipid-laden macrophages induce extracellular matrix degradation, while lipid uptake eventually causes their death with formation of a necrotic core. The efficiency in clearance of dead cells by phagocytes (efferocytosis), can also be considered as a determinant of plaque vulnerability. An important feature of macrophages is their great plasticity and functional diversity in response to signals from the plaque microenvironment. Several such 'signals' (cholesterol, oxidative stress, hypoxia, cytokines...) can in fact modulate cell differentiation at transcriptional and epigenetic levels, thus altering the balance between the effector vs. reparative functions of macrophages. A whole gamut of specific subsets are thus originated, which appear to be simultaneously present in lesions with proportions that vary according to their location, the disease stage, and the presence of additional cell types such as e.g. dendritic cells. The result is a multiplicity of potential pharmacological targets, representing a major obstacle for the devisement of therapeutic strategies. Experimental approaches have been attempted in diverse directions: e.g. modulating the macrophage phenotype to an anti-inflammatory and resolving state, or blocking pro-inflammatory cytokines that macrophages produce, or alternatively enhancing efferocytosis in order to favour the resolution of inflammation and stabilization of plaques. Blocking monocyte recruitment was proposed in order to hinder the initial steps of atherogenesis. Other treatments were aimed to inhibiting local proliferation of pro-inflammatory macrophages. Specific targeting of macrophages has however to date not yet provided significant, translational results. The present Research Topic collects articles to help unravel the complexity of macrophage behaviour in atherosclerosis and identify innovative pharmacological approaches.

With contributions by numerous experts