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Seminars in Immunopathology Aug 2021Liver disorders due to infections are a substantial health concern in underdeveloped and industrialized countries. This includes not only hepatotropic viruses (e.g.,... (Review)
Review
Liver disorders due to infections are a substantial health concern in underdeveloped and industrialized countries. This includes not only hepatotropic viruses (e.g., hepatitis B, hepatitis C) but also bacterial and parasitic infections such as amebiasis, leishmaniasis, schistosomiasis, or echinococcosis. Recent studies of the immune mechanisms underlying liver disease show that monocytes play an essential role in determining patient outcomes. Monocytes are derived from the mononuclear phagocyte lineage in the bone marrow and are present in nearly all tissues of the body; these cells function as part of the early innate immune response that reacts to challenge by external pathogens. Due to their special ability to develop into tissue macrophages and dendritic cells and to change from an inflammatory to an anti-inflammatory phenotype, monocytes play a pivotal role in infectious and non-infectious liver diseases: they can maintain inflammation and support resolution of inflammation. Therefore, tight regulation of monocyte recruitment and termination of monocyte-driven immune responses in the liver is prerequisite to appropriate healing of organ damage. In this review, we discuss monocyte-dependent immune mechanisms underlying hepatic infectious disorders. Better understanding of these immune mechanisms may lead to development of new interventions to treat acute liver disease and prevent progression to organ failure.
Topics: Humans; Immunity, Innate; Liver Diseases; Macrophages; Monocytes
PubMed: 33829283
DOI: 10.1007/s00281-021-00852-1 -
Current Biology : CB Jan 2021New work shows that the glycocalyx meshwork on the surface of macrophages prevents phagocytic receptors from binding their ligands by two meansĀ - electrostatic charge...
New work shows that the glycocalyx meshwork on the surface of macrophages prevents phagocytic receptors from binding their ligands by two meansĀ - electrostatic charge and steric hindrance. Components of this barrier are present on pathogenic and malignant targets that elude phagocytosis.
Topics: Glycocalyx; Ligands; Macrophages; Phagocytes; Phagocytosis
PubMed: 33434480
DOI: 10.1016/j.cub.2020.10.066 -
Nephron 2022Various forms of cell death have been identified, and billions of cells die during development and daily in adult organisms. Clearing dead cells and associated cellular... (Review)
Review
Various forms of cell death have been identified, and billions of cells die during development and daily in adult organisms. Clearing dead cells and associated cellular debris is an integral part of tissue homeostasis. While diverse types of phagocytes remove various forms of dying cells during acute kidney injury (AKI), it remains unknown whether boosting removal of a specific form of dying cell would provide a benefit and which cell type should be targeted for phagocytosis-mediated therapy. As there is a lack of viable strategies for the prevention and treatment of AKI, novel therapies and innovative approaches are required. There is a strong demand on developing and analyzing novel models to boost, monitor, and stop phagocytosis of dying cells.
Topics: Acute Kidney Injury; Apoptosis; Cell Death; Female; Humans; Male; Phagocytes; Phagocytosis
PubMed: 34284391
DOI: 10.1159/000517731 -
Nephron 2023Myeloid cells form an important element of the response to ischemia-reperfusion injury (IRI). While the mononuclear phagocyte system is complex and difficult to study,... (Review)
Review
BACKGROUND
Myeloid cells form an important element of the response to ischemia-reperfusion injury (IRI). While the mononuclear phagocyte system is complex and difficult to study, our knowledge of the cells involved and their impacts has been steadily increasing. However, there is still need to rigorously define and separate the functions of discreet myeloid populations in the kidney. The relatively recent distinction between resident macrophages and infiltrating monocytes in the kidney is an important advance that will enhance our understanding of the various roles of distinct myeloid populations, but specific tools are needed to rigorously define the contributions of each to injury, repair, and the transition to chronic disease.
SUMMARY
Resident macrophages in the kidney form a network with various supportive roles during development and homeostasis. While the classification of these cells has been frequently convoluted in the literature, evidence for their roles during injury and repair is starting to accumulate. Current indications suggest they may have a minimal role during injury processes but may be important during the recovery phase. However, their involvement may also be dependent on their activation state in response to environmental cues. Investigations of the M1/M2 phenotype of myeloid cells have shed some light on the phenotypes that contribute to the manifestation of injury and/or recovery, but it is still difficult to form detailed conclusions. Here we will discuss the potential involvement of resident cells in these processes and the use of the M1/M2 system for defining the myeloid response following IRI.
KEY MESSAGES
There is a need for additional specific analysis of the contribution of resident versus recruited myeloid cells to injury, recovery, and chronic disease in the kidney. In addition, the contribution of myeloid activation states that extend beyond simple M1/M2 classification is an important area that needs close attention. Our ability to assess resident cells is growing, and awareness of the shortcoming of the M1/M2 system is also increasing. These are promising developments which bode well for the future of kidney injury and disease research.
Topics: Humans; Acute Kidney Injury; Kidney; Macrophages; Monocytes; Reperfusion Injury
PubMed: 36108596
DOI: 10.1159/000526266 -
International Journal of Molecular... Aug 2022In the field of science, technology and medicine, carbon-based nanomaterials and nanoparticles (CNMs) are becoming attractive nanomaterials that are increasingly used.... (Review)
Review
In the field of science, technology and medicine, carbon-based nanomaterials and nanoparticles (CNMs) are becoming attractive nanomaterials that are increasingly used. However, it is important to acknowledge the risk of nanotoxicity that comes with the widespread use of CNMs. CNMs can enter the body via inhalation, ingestion, intravenously or by any other route, spread through the bloodstream and penetrate tissues where (in both compartments) they interact with components of the immune system. Like invading pathogens, CNMs can be recognized by large numbers of receptors that are present on the surface of innate immune cells, notably monocytes and macrophages. Depending on the physicochemical properties of CNMs, i.e., shape, size, or adsorbed contamination, phagocytes try to engulf and process CNMs, which might induce pro/anti-inflammatory response or lead to modulation and disruption of basic immune activity. This review focuses on existing data on the immunotoxic potential of CNMs, particularly in professional phagocytes, as they play a central role in processing and eliminating foreign particles. The results of immunotoxic studies are also described in the context of the entry routes, impacts of contamination and means of possible elimination. Mechanisms of proinflammatory effect depending on endocytosis and intracellular distribution of CNMs are highlighted as well.
Topics: Carbon; Macrophages; Nanostructures
PubMed: 36012161
DOI: 10.3390/ijms23168889 -
Immunological Reviews Oct 2023The clearance of dead and dying cells, termed efferocytosis, is a rapid and efficient process and one that is critical for organismal health. The extraordinary speed and... (Review)
Review
The clearance of dead and dying cells, termed efferocytosis, is a rapid and efficient process and one that is critical for organismal health. The extraordinary speed and efficiency with which dead cells are detected and engulfed by immune cells within tissues presents a challenge to researchers who wish to unravel this fascinating process, since these fleeting moments of uptake are almost impossible to catch in vivo. In recent years, the fruit fly (Drosophila melanogaster) embryo has emerged as a powerful model to circumvent this problem. With its abundance of dying cells, specialist phagocytes and relative ease of live imaging, the humble fly embryo provides a unique opportunity to catch and study the moment of cell engulfment in real-time within a living animal. In this review, we explore the recent advances that have come from studies in the fly, and how live imaging and genetics have revealed a previously unappreciated level of diversity in the efferocytic program. A variety of efferocytic strategies across the phagocytic cell population ensure efficient and rapid clearance of corpses wherever death is encountered within the varied and complex setting of a multicellular living organism.
Topics: Animals; Humans; Drosophila melanogaster; Apoptosis; Phagocytosis; Phagocytes; Drosophila
PubMed: 37589239
DOI: 10.1111/imr.13266 -
Nature Cell Biology Dec 2019Apoptotic cell clearance (efferocytosis) elicits an anti-inflammatory response by phagocytes, but the mechanisms that underlie this response are still being defined....
Apoptotic cell clearance (efferocytosis) elicits an anti-inflammatory response by phagocytes, but the mechanisms that underlie this response are still being defined. Here, we uncover a chloride-sensing signalling pathway that controls both the phagocyte 'appetite' and its anti-inflammatory response. Efferocytosis transcriptionally altered the genes that encode the solute carrier (SLC) proteins SLC12A2 and SLC12A4. Interfering with SLC12A2 expression or function resulted in a significant increase in apoptotic corpse uptake per phagocyte, whereas the loss of SLC12A4 inhibited corpse uptake. In SLC12A2-deficient phagocytes, the canonical anti-inflammatory program was replaced by pro-inflammatory and oxidative-stress-associated gene programs. This 'switch' to pro-inflammatory sensing of apoptotic cells resulted from the disruption of the chloride-sensing pathway (and not due to corpse overload or poor degradation), including the chloride-sensing kinases WNK1, OSR1 and SPAK-which function upstream of SLC12A2-had a similar effect on efferocytosis. Collectively, the WNK1-OSR1-SPAK-SLC12A2/SLC12A4 chloride-sensing pathway and chloride flux in phagocytes are key modifiers of the manner in which phagocytes interpret the engulfed apoptotic corpse.
Topics: Animals; Apoptosis; Biological Transport; Cell Line; Cell Line, Tumor; Chlorides; Humans; Inflammation; Jurkat Cells; Mice; Mice, Inbred C57BL; Oxidative Stress; Phagocytes; Phagocytosis; Signal Transduction; Sodium-Potassium-Chloride Symporters; Transcription, Genetic
PubMed: 31792382
DOI: 10.1038/s41556-019-0431-1 -
Frontiers in Immunology 2023Mononuclear phagocytes (MP), i.e., monocytes, macrophages, and dendritic cells (DCs), are essential for immune homeostasis via their capacities to clear pathogens,... (Review)
Review
Mononuclear phagocytes (MP), i.e., monocytes, macrophages, and dendritic cells (DCs), are essential for immune homeostasis via their capacities to clear pathogens, pathogen components, and non-infectious particles. However, tissue injury-related changes in local microenvironments activate resident and infiltrating MP towards pro-inflammatory phenotypes that contribute to inflammation by secreting additional inflammatory mediators. Efficient control of injurious factors leads to a switch of MP phenotype, which changes the microenvironment towards the resolution of inflammation. In the same way, MP endorses adaptive structural responses leading to either compensatory hypertrophy of surviving cells, tissue regeneration from local tissue progenitor cells, or tissue fibrosis and atrophy. Under certain circumstances, MP contribute to the reversal of tissue fibrosis by clearance of the extracellular matrix. Here we give an update on the tissue microenvironment-related factors that, upon tissue injury, instruct resident and infiltrating MP how to support host defense and recover tissue function and integrity. We propose that MP are not intrinsically active drivers of organ injury and dysfunction but dynamic amplifiers (and biomarkers) of specific tissue microenvironments that vary across spatial and temporal contexts. Therefore, MP receptors are frequently redundant and suboptimal targets for specific therapeutic interventions compared to molecular targets upstream in adaptive humoral or cellular stress response pathways that influence tissue milieus at a contextual level.
Topics: Humans; Macrophages; Monocytes; Fibrosis; Inflammation; Atrophy
PubMed: 37868987
DOI: 10.3389/fimmu.2023.1194988 -
Redox Biology Aug 2023Reactive oxygen species (ROS) are a family of highly reactive molecules with numerous, often pleiotropic functions within the cell and the organism. Due to their... (Review)
Review
Reactive oxygen species (ROS) are a family of highly reactive molecules with numerous, often pleiotropic functions within the cell and the organism. Due to their potential to destroy biological structures such as membranes, enzymes and organelles, ROS have long been recognized as harmful yet unavoidable by-products of cellular metabolism leading to "oxidative stress" unless counterbalanced by cellular anti-oxidative defense mechanisms. Phagocytes utilize this destructive potential of ROS released in high amounts to defend against invading pathogens. In contrast, a regulated and fine-tuned release of "signaling ROS" (sROS) provides essential intracellular second messengers to modulate central aspects of immunity, including antigen presentation, activation of antigen presenting cells (APC) as well as the APC:T cell interaction during T cell activation. This regulated release of sROS is foremost attributed to the specialized enzyme NADPH-oxidase (NOX) 2 expressed mainly in myeloid cells such as neutrophils, macrophages and dendritic cells (DC). NOX-2-derived sROS are primarily involved in immune regulation and mediate protection against autoimmunity as well as maintenance of self-tolerance. Consequently, deficiencies in NOX2 not only result in primary immune-deficiencies such as Chronic Granulomatous Disease (CGD) but also lead to auto-inflammatory diseases and autoimmunity. A comprehensive understanding of NOX2 activation and regulation will be key for successful pharmaceutical interventions of such ROS-related diseases in the future. In this review, we summarize recent progress regarding immune regulation by NOX2-derived ROS and the consequences of its deregulation on the development of immune disorders.
Topics: Humans; Reactive Oxygen Species; NADPH Oxidases; Neutrophils; Granulomatous Disease, Chronic; Phagocytes
PubMed: 37379662
DOI: 10.1016/j.redox.2023.102795 -
Immunological Reviews Mar 2023Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating... (Review)
Review
Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating mechanisms is phagocytosis, the process of particle engulfment into a vacuole-like structure called the phagosome. The antimicrobial activity of the phagocytic process results from a collaboration of multiple systems and mechanisms within this organelle, where a complex interplay of ion fluxes, pH, reactive oxygen species, and antimicrobial proteins creates a dynamic antimicrobial environment. This complexity, combined with the difficulties of studying neutrophils ex vivo, has led to gaps in our knowledge of how the neutrophil phagosome optimizes pathogen killing. In particular, controversy has arisen regarding the relative contribution and integration of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived antimicrobial agents and granule-delivered antimicrobial proteins. Clinical syndromes arising from dysfunction in these systems in humans allow useful insight into these mechanisms, but their redundancy and synergy add to the complexity. In this article, we review the current knowledge regarding the formation and function of the neutrophil phagosome, examine new insights into the phagosomal environment that have been permitted by technological advances in recent years, and discuss aspects of the phagocytic process that are still under debate.
Topics: Humans; Neutrophils; Phagosomes; Phagocytosis; Phagocytes; Reactive Oxygen Species
PubMed: 36440666
DOI: 10.1111/imr.13173