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Journal of Leukocyte Biology Jan 2019Phagocytes are cells of the immune system that play important roles in phagocytosis, respiratory burst and degranulation-key components of innate immunity and response... (Review)
Review
Phagocytes are cells of the immune system that play important roles in phagocytosis, respiratory burst and degranulation-key components of innate immunity and response to infection. This diverse group of cells includes monocytes, macrophages, dendritic cells, neutrophils, eosinophils, and basophils-heterogeneous cell populations possessing cell and tissue-specific functions of which cellular metabolism comprises a critical underpinning. Core functions of phagocytic cells are diverse and sensitive to alterations in environmental- and tissue-specific nutrients and growth factors. As phagocytic cells adapt to these extracellular cues, cellular processes are altered and may contribute to pathogenesis. The considerable degree of functional heterogeneity among monocyte, neutrophil, and other phagocytic cell populations necessitates diverse metabolism. As we review our current understanding of metabolism in phagocytic cells, gaps are focused on to highlight the need for additional studies that hopefully enable improved cell-based strategies for counteracting cancer and other diseases.
Topics: Adaptation, Physiological; Animals; Humans; Macrophages; Metabolic Networks and Pathways; Neoplasms; Neutrophils; Phagocytes
PubMed: 30247792
DOI: 10.1002/JLB.4RI0518-195R -
Cell Reports Feb 2023The diversity of mononuclear phagocyte (MNP) subpopulations across tissues is one of the key physiological characteristics of the immune system. Here, we focus on...
The diversity of mononuclear phagocyte (MNP) subpopulations across tissues is one of the key physiological characteristics of the immune system. Here, we focus on understanding the metabolic variability of MNPs through metabolic network analysis applied to three large-scale transcriptional datasets: we introduce (1) an ImmGen MNP open-source dataset of 337 samples across 26 tissues; (2) a myeloid subset of ImmGen Phase I dataset (202 MNP samples); and (3) a myeloid mouse single-cell RNA sequencing (scRNA-seq) dataset (51,364 cells) assembled based on Tabula Muris Senis. To analyze such large-scale datasets, we develop a network-based computational approach, genes and metabolites (GAM) clustering, for unbiased identification of the key metabolic subnetworks based on transcriptional profiles. We define 9 metabolic subnetworks that encapsulate the metabolic differences within MNP from 38 different tissues. Obtained modules reveal that cholesterol synthesis appears particularly active within the migratory dendritic cells, while glutathione synthesis is essential for cysteinyl leukotriene production by peritoneal and lung macrophages.
Topics: Animals; Mice; Phagocytes; Single-Cell Analysis
PubMed: 36708514
DOI: 10.1016/j.celrep.2023.112046 -
Developmental Cell Jul 2016Phagocytes recognize and eliminate pathogens, alert other tissues of impending threats, and provide a link between innate and adaptive immunity. They also maintain... (Review)
Review
Phagocytes recognize and eliminate pathogens, alert other tissues of impending threats, and provide a link between innate and adaptive immunity. They also maintain tissue homeostasis, consuming dead cells without causing alarm. The receptor engagement, signal transduction, and cytoskeletal rearrangements underlying phagocytosis are paradigmatic of other immune responses and bear similarities to macropinocytosis and cell migration. We discuss how the glycocalyx restricts access to phagocytic receptors, the processes that enable receptor engagement and clustering, and the remodeling of the actin cytoskeleton that controls the mobility of membrane proteins and lipids and provides the mechanical force propelling the phagocyte membrane toward and around the phagocytic prey.
Topics: Actin Cytoskeleton; Animals; Biophysics; Cell Movement; Diffusion; Humans; Phagocytes; Phagocytosis; Signal Transduction
PubMed: 27459066
DOI: 10.1016/j.devcel.2016.06.023 -
Seminars in Immunopathology Nov 2018Post-transplant immunosuppression has reduced the incidence of T cell-mediated acute rejection, yet long-term cardiac graft survival rates remain a challenge. An... (Review)
Review
Post-transplant immunosuppression has reduced the incidence of T cell-mediated acute rejection, yet long-term cardiac graft survival rates remain a challenge. An important determinant of chronic solid organ allograft complication is accelerated vascular disease of the transplanted graft. In the case of cardiac allograft vasculopathy (CAV), the precise cellular etiology remains inadequately understood; however, histologic evidence hints at the accumulation and activation of innate phagocytes as a causal contributing factor. This includes monocytes, macrophages, and immature dendritic cell subsets. In addition to crosstalk with adaptive T and B immune cells, myeloid phagocytes secrete paracrine signals that directly activate fibroblasts and vascular smooth muscle cells, both of which contribute to fibrous intimal thickening. Though maladaptive phagocyte functions may promote CAV, directed modulation of myeloid cell function, at the molecular level, holds promise for tolerance and prolonged cardiac graft function.
Topics: Acute Disease; Animals; Antigens, Differentiation; CD47 Antigen; Cell Communication; Chronic Disease; Endocytosis; Graft Rejection; Heart Transplantation; Humans; Hypoxia; Immunity, Innate; Isoantigens; Phagocytes; Receptors, Immunologic; Signal Transduction; T-Lymphocytes; Vascular Diseases
PubMed: 30141073
DOI: 10.1007/s00281-018-0699-4 -
Trends in Immunology Jun 2017Recognition of microbial pathogens and dead cells and their phagocytic uptake by specialized immune cells are essential to maintain host homeostasis. Phagosomes undergo... (Review)
Review
Recognition of microbial pathogens and dead cells and their phagocytic uptake by specialized immune cells are essential to maintain host homeostasis. Phagosomes undergo fusion and fission events with endosomal and lysosomal compartments, a process called 'phagosome maturation', which leads to the degradation of the phagosomal content. However, many phagocytic cells also act as antigen-presenting cells and must balance degradation and peptide preservation. Emerging evidence indicates that receptor engagement by phagosomal cargo, as well as inflammatory mediators and cellular activation affect many aspects of phagosome maturation. Unsurprisingly, pathogens have developed strategies to hijack this machinery, thereby interfering with host immunity. Here, we highlight progress in this field, summarize findings on the impact of immune signals, and discuss consequences for pathogen elimination.
Topics: Animals; Antigen Presentation; Cell Differentiation; Endosomes; Humans; Immunity, Innate; Inflammation; Lysosomes; Membrane Fusion; Phagocytes; Phagosomes; Proteolysis; Receptors, Pattern Recognition; Signal Transduction
PubMed: 28416446
DOI: 10.1016/j.it.2017.03.006 -
Trends in Immunology Oct 2017The life of an organism requires the assistance of an unlikely process: programmed cell death. Both development and the maintenance of homeostasis result in the... (Review)
Review
The life of an organism requires the assistance of an unlikely process: programmed cell death. Both development and the maintenance of homeostasis result in the production of superfluous cells that must eventually be disposed of. Furthermore, programmed cell death can also represent a defense mechanism; for example, by depriving pathogens of a replication niche. The responsibility of handling these dead cells falls on phagocytes of the immune system, which surveil their surroundings for dying or dead cells and efficiently clear them in a quiescent manner. This process, termed efferocytosis, depends on cooperation between the phagocyte and the dying cell. In this review we explore different types of programmed cell death and their impact on innate immune responses.
Topics: Animals; Apoptosis; Homeostasis; Humans; Immune System; Immunity, Innate; Inflammation; Mononuclear Phagocyte System; Phagocytes; Phagocytosis
PubMed: 28734635
DOI: 10.1016/j.it.2017.06.009 -
American Journal of Physiology. Renal... Apr 2017Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been... (Review)
Review
Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the present knowledge regarding classification of these cells in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases.
Topics: Acute Kidney Injury; Animals; Biomarkers; Cell Plasticity; Fibrosis; Humans; Inflammation Mediators; Kidney; Mice; Nephritis; Phagocytes; Phenotype; Receptors, Immunologic; Signal Transduction
PubMed: 28100500
DOI: 10.1152/ajprenal.00369.2016 -
Pharmacological Research May 2023Nicotinic acetylcholine receptors are not only expressed by the nervous system and at the neuro-muscular junction but also by mononuclear phagocytes, which belong to the... (Review)
Review
Nicotinic acetylcholine receptors are not only expressed by the nervous system and at the neuro-muscular junction but also by mononuclear phagocytes, which belong to the innate immune system. Mononuclear phagocyte is an umbrella term for monocytes, macrophages, and dendritic cells. These cells play pivotal roles in host defense against infection but also in numerous often debilitating diseases that are characterized by exuberant inflammation. Nicotinic acetylcholine receptors of the neuronal type dominate in these cells, and their stimulation is mainly associated with anti-inflammatory effects. Although the cholinergic modulation of mononuclear phagocytes is of eminent clinical relevance for the prevention and treatment of inflammatory diseases and neuropathic pain, we are only beginning to understand the underlying mechanisms on the molecular level. The purpose of this review is to report and critically discuss the current knowledge on signal transduction mechanisms elicited by nicotinic acetylcholine receptors in mononuclear phagocytes.
Topics: Humans; Receptors, Nicotinic; Macrophages; Monocytes; Signal Transduction; Inflammation
PubMed: 36966897
DOI: 10.1016/j.phrs.2023.106727 -
Microbiology Spectrum Oct 2016Monocytes are short-lived mononuclear phagocytes that circulate in the bloodstream and comprise two main subpopulations that in the mouse are best defined by the Ly6C... (Review)
Review
Monocytes are short-lived mononuclear phagocytes that circulate in the bloodstream and comprise two main subpopulations that in the mouse are best defined by the Ly6C marker. Intravascular functions of "classical" Ly6C+ monocytes and their interactions with other lymphoid and myeloid leukocytes in the circulation remain poorly understood. Rather, these cells are known to efficiently extravasate into tissues. Indeed, Ly6C+ monocytes and their descendants have emerged as a third, highly plastic and dynamic cellular system that complements the two classical, tissue-resident mononuclear phagocyte compartments, i.e., macrophages and dendritic cells, on demand. Following recruitment to injured tissue, Ly6C+ monocytes respond to local cues and can critically contribute to the initiation and resolution of inflammatory reactions. The second main murine monocyte subset, Ly6C- cells, derive in steady state from Ly6C+ monocytes and remain in the vasculature, where the cells act as scavengers. Moreover, a major fraction of Ly6C- monocytes adheres to the capillary endothelium and patrols the vessel wall for surveillance. Given the central role of monocytes in homeostasis and pathology, in-depth study of this cellular compartment can be highly informative on the health state of the organism and provides an attractive target for therapeutic intervention.
Topics: Animals; Dendritic Cells; Macrophages; Mice; Monocytes
PubMed: 27780020
DOI: 10.1128/microbiolspec.MCHD-0033-2016 -
Immunological Reviews Sep 2016The engulfment of apoptotic cells by phagocytes, a process referred to as efferocytosis, is essential for maintenance of normal tissue homeostasis and a prerequisite for... (Review)
Review
The engulfment of apoptotic cells by phagocytes, a process referred to as efferocytosis, is essential for maintenance of normal tissue homeostasis and a prerequisite for the resolution of inflammation. Neutrophils are the predominant circulating white blood cell in humans, and contain an arsenal of toxic substances that kill and degrade microbes. Neutrophils are short-lived and spontaneously die by apoptosis. This review will highlight how the engulfment of apoptotic neutrophils by human phagocytes occurs, how heterogeneity of phagocyte populations influences efferocytosis signaling, and downstream consequences of efferocytosis. The efferocytosis of apoptotic neutrophils by macrophages promotes anti-inflammatory signaling, prevents neutrophil lysis, and dampens immune responses. Given the immunomodulatory properties of efferocytosis, understanding pathways that regulate and enhance efferocytosis could be harnessed to combat infection and chronic inflammatory conditions.
Topics: Animals; Apoptosis; Humans; Immunity, Innate; Immunomodulation; Inflammation; Macrophages; Neutrophils; Phagocytosis; Signal Transduction
PubMed: 27558346
DOI: 10.1111/imr.12453