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Advances in Experimental Medicine and... 2020Dictyostelium cells are professional phagocytes that are capable of handling particles of variable shapes and sizes. Here we offer long bacteria that challenge the...
Dictyostelium cells are professional phagocytes that are capable of handling particles of variable shapes and sizes. Here we offer long bacteria that challenge the uptake mechanism to its limits and report on the responses of the phagocytes if they are unable to engulf the particle by closing the phagocytic cup. Reasons for failure may be a length of the particle much larger than the phagocyte's diameter, or competition with another phagocyte. A cell may simultaneously release a particle and engulf another one. The final phase of release can be fast, causing the phagosome membrane to turn inside-out and to form a bleb. Myosin-II may be involved in the release by generating tension at the plasma membrane, it does however not accumulate on the phagosome to act there directly in expelling the particle. Labeling with GFP-2FYVE indicates that processing of the phagosome with phosphatidylinositol 3-phosphate begins at the base of a long phagosome already before closure of the cup. The decision of releasing the particle can be made even at the stage of the processed phagosome.
Topics: Bacteria; Dictyostelium; Phagocytes; Phagocytosis; Phagosomes
PubMed: 32399826
DOI: 10.1007/978-3-030-40406-2_5 -
Pflugers Archiv : European Journal of... Jun 2022Ischemic retinopathies (IR) are vision-threatening diseases that affect a substantial amount of people across all age groups worldwide. The current treatment options of... (Review)
Review
Ischemic retinopathies (IR) are vision-threatening diseases that affect a substantial amount of people across all age groups worldwide. The current treatment options of photocoagulation and anti-VEGF therapy have side effects and are occasionally unable to prevent disease progression. It is therefore worthwhile to consider other molecular targets for the development of novel treatment strategies that could be safer and more efficient. During the manifestation of IR, the retina, normally an immune privileged tissue, encounters enhanced levels of cellular stress and inflammation that attract mononuclear phagocytes (MPs) from the blood stream and activate resident MPs (microglia). Activated MPs have a multitude of effects within the retinal tissue and have the potential to both counter and exacerbate the harmful tissue microenvironment. The present review discusses the current knowledge about the role of inflammation and activated retinal MPs in the major IRs: retinopathy of prematurity and diabetic retinopathy. We focus particularly on MPs and their secreted factors and cell-cell-based interactions between MPs and endothelial cells. We conclude that activated MPs play a major role in the manifestation and progression of IRs and could therefore become a promising new target for novel pharmacological intervention strategies in these diseases.
Topics: Endothelial Cells; Humans; Infant, Newborn; Inflammation; Ischemia; Neovascularization, Pathologic; Phagocytes; Retina; Retinal Diseases
PubMed: 35524802
DOI: 10.1007/s00424-022-02695-7 -
Nature Reviews. Immunology May 2021Cell death occurs when a pathogen invades a host organism or the organism is subjected to sterile injury. Thus, cell death is often closely associated with the induction... (Review)
Review
Cell death occurs when a pathogen invades a host organism or the organism is subjected to sterile injury. Thus, cell death is often closely associated with the induction of an immune response. Furthermore, cell death can occur as a consequence of the immune response and precedes the tissue renewal and repair responses that are initiated by innate immune cells during resolution of an immune response. Beyond immunity, cell death is required for development, morphogenesis and homeostasis. How can such a ubiquitous event as cell death trigger such a wide range of context-specific effector responses? Dying cells are sensed by innate immune cells using specialized receptors and phagocytosed through a process termed efferocytosis. Here, we outline a general principle whereby signals within the dead cell as well as the environment are integrated by specific efferocytes to define the appropriate effector response.
Topics: Animals; Cell Death; Cellular Microenvironment; Cytokines; Homeostasis; Host-Pathogen Interactions; Humans; Immunity, Innate; Mathematical Concepts; Models, Immunological; Phagocytes; Phagocytosis; Signal Transduction
PubMed: 33188303
DOI: 10.1038/s41577-020-00456-0 -
Cold Spring Harbor Perspectives in... Apr 2020Multicellular organisms are not created through cell proliferation alone. It is through cell death that an indefinite cellular mass is pared back to reveal its true... (Review)
Review
Multicellular organisms are not created through cell proliferation alone. It is through cell death that an indefinite cellular mass is pared back to reveal its true form. Cells are also lost throughout life as part of homeostasis and through injury. This detritus represents a significant burden to the living organism and must be cleared, most notably through the use of specialized phagocytic cells. Our understanding of these phagocytes and how they engulf cell corpses has been greatly aided by studying the fruit fly, Here we review the contribution of research to our understanding of how phagocytes respond to cell death. We focus on the best studied phagocytes in the fly: the glia of the central nervous system, the ovarian follicle cells, and the macrophage-like hemocytes. Each is explored in the context of the tissue they maintain as well as how they function during development and in response to injury.
Topics: Animals; Apoptosis; Astrocytes; Cell Death; Cell Proliferation; Central Nervous System; Drosophila Proteins; Drosophila melanogaster; Female; Hemocytes; Homeostasis; Inflammation; Macrophages; Neuroglia; Ovarian Follicle; Phagocytes; Phagocytosis
PubMed: 31501193
DOI: 10.1101/cshperspect.a036350 -
Methods in Molecular Biology (Clifton,... 2020The process of neutrophil apoptosis has an important role in the resolution of acute inflammation. Apoptotic cell death is characterized by a coordinated sequence of...
The process of neutrophil apoptosis has an important role in the resolution of acute inflammation. Apoptotic cell death is characterized by a coordinated sequence of cellular alterations that serve to uncouple neutrophil effector functions whilst maintaining plasma membrane integrity. In this way the release on neutrophil intracellular contents, including proteases, glycosidases, and reactive oxygen species, is limited during apoptosis. In addition, plasma membrane alterations associated with neutrophil apoptosis provide molecular cues that enable recognition by phagocytic cells, including macrophages. The recognition and uptake of apoptotic neutrophils by macrophages dampens proinflammatory responses to pathogen- or damage-associated molecular patterns and triggers release of proresolution mediators, that further promote resolution of inflammation. The key cellular and molecular events that act to control neutrophil apoptosis and subsequent macrophage phagocytosis have been characterized by in vitro studies, unveiling potential therapeutic targets for the manipulation of these regulatory pathways. In this chapter, we outline some of the key assays that are used to assess neutrophil apoptosis in vitro, together with methods to assess activation of the apoptotic machinery and phagocytic clearance of apoptotic neutrophils.
Topics: Apoptosis; Caspases; Cell Membrane; DNA Fragmentation; Flow Cytometry; Humans; Membrane Potential, Mitochondrial; Mitochondria; Neutrophils; Phagocytes; Phagocytosis; Phosphatidylserines; Reactive Oxygen Species
PubMed: 31728991
DOI: 10.1007/978-1-0716-0154-9_13 -
Trends in Immunology Feb 2023There are striking similarities between the sea urchin cavity macrophage-like phagocytes (coelomocytes) and mammalian cavity macrophages in not only their location, but... (Review)
Review
There are striking similarities between the sea urchin cavity macrophage-like phagocytes (coelomocytes) and mammalian cavity macrophages in not only their location, but also their behaviors. These cells are crucial for maintaining homeostasis within the cavity following a breach, filling the gap and functioning as a barrier between vital organs and the environment. In this review, we summarize the evolving literature regarding these Gata6 large peritoneal macrophages (GLPMs), focusing on ontogeny, their responses to perturbations, including their rapid aggregation via coagulation, as well as scavenger receptor cysteine-rich domains and their potential roles in diseases, such as cancer. We challenge the 50-year old phenomenon of the 'macrophage disappearance reaction' (MDR) and propose the new term 'macrophage disturbance of homeostasis reaction' (MDHR), which may better describe this complex phenomenon.
Topics: Animals; GATA6 Transcription Factor; Macrophages, Peritoneal; Mammals; Phagocytes; Sea Urchins
PubMed: 36623953
DOI: 10.1016/j.it.2022.12.002 -
Frontiers in Immunology 2021Phagocytosis is the cellular defense mechanism used to eliminate antigens derived from dysregulated or damaged cells, and microbial pathogens. Phagocytosis is therefore...
Phagocytosis is the cellular defense mechanism used to eliminate antigens derived from dysregulated or damaged cells, and microbial pathogens. Phagocytosis is therefore a pillar of innate immunity, whereby foreign particles are engulfed and degraded in lysolitic vesicles. In hexacorallians, phagocytic mechanisms are poorly understood, though putative anthozoan phagocytic cells (amoebocytes) have been identified histologically. We identify and characterize phagocytes from the coral and the sea anemone . Using fluorescence-activated cell sorting and microscopy, we show that distinct populations of phagocytic cells engulf bacteria, fungal antigens, and beads. In addition to pathogenic antigens, we show that phagocytic cells engulf self, damaged cells. We show that target antigens localize to low pH phagolysosomes, and that degradation is occurring within them. Inhibiting actin filament rearrangement interferes with efficient particle phagocytosis but does not affect small molecule pinocytosis. We also demonstrate that cellular markers for lysolitic vesicles and reactive oxygen species (ROS) correlate with hexacorallian phagocytes. These results establish a foundation for improving our understanding of hexacorallian immune cell biology.
Topics: Animals; Anthozoa; Biomarkers; Cytokines; Cytoplasmic Vesicles; Flow Cytometry; Hydrogen-Ion Concentration; Immunity, Innate; Phagocytes; Phagocytosis; Phagosomes; Sea Anemones
PubMed: 34381444
DOI: 10.3389/fimmu.2021.662803 -
Frontiers in Immunology 2020
Topics: Animals; Phagocytes
PubMed: 33362804
DOI: 10.3389/fimmu.2020.628847 -
Current Opinion in Cell Biology Oct 2020Phagocytosis is a widespread and evolutionarily conserved process with diverse biological functions, ranging from engulfment of invading microbes during infection to... (Review)
Review
Phagocytosis is a widespread and evolutionarily conserved process with diverse biological functions, ranging from engulfment of invading microbes during infection to clearance of apoptotic debris in tissue homeostasis. Along with differences in biochemical composition, phagocytic targets greatly differ in physical attributes, such as size, shape, and rigidity, which are now recognized as important regulators of this process. Force exertion at the cell-target interface and cellular mechanical changes during phagocytosis are emerging as crucial factors underlying sensing of such target properties. With technological developments, mechanical aspects of phagocytosis are increasingly accessible experimentally, revealing remarkable organizational complexity of force exertion. An increasingly high-resolution picture is emerging of how target physical cues and cellular mechanical properties jointly govern important steps throughout phagocytic engulfment.
Topics: Animals; Biophysical Phenomena; Mechanotransduction, Cellular; Phagocytes; Phagocytosis
PubMed: 32698097
DOI: 10.1016/j.ceb.2020.05.011 -
Frontiers in Immunology 2020The spirochetal bacteria spp. are causative agents of leptospirosis, a globally neglected and reemerging zoonotic disease. Infection with these pathogens may lead to an... (Review)
Review
The spirochetal bacteria spp. are causative agents of leptospirosis, a globally neglected and reemerging zoonotic disease. Infection with these pathogens may lead to an acute and potentially fatal disease but also to chronic asymptomatic renal colonization. Both forms of disease demonstrate the ability of leptospires to evade the immune response of their hosts. In this review, we aim first to recapitulate the knowledge and explore the controversial data about the opsonization, recognition, intracellular survival, and killing of leptospires by scavenger cells, including platelets, neutrophils, macrophages, and dendritic cells. Second, we will summarize the known specificities of the recognition or escape of leptospire components (the so-called microbial-associated molecular patterns; MAMPs) by the pattern recognition receptors (PRRs) of the Toll-like and NOD-like families. These PRRs are expressed by phagocytes, and their stimulation by MAMPs triggers pro-inflammatory cytokine and chemokine production and bactericidal responses, such as antimicrobial peptide secretion and reactive oxygen species production. Finally, we will highlight recent studies suggesting that boosting or restoring phagocytic functions by treatments using agonists of the Toll-like or NOD receptors represents a novel prophylactic strategy and describe other potential therapeutic or vaccine strategies to combat leptospirosis.
Topics: Animals; Humans; Immune Evasion; Immunity, Innate; Leptospira; Leptospirosis; Macrophages; NLR Proteins; Neutrophils; Phagocytes; Phagocytosis; Toll-Like Receptors
PubMed: 33123147
DOI: 10.3389/fimmu.2020.571816