-
Current Opinion in Neurobiology Dec 2013In the developing nervous system, synaptic connections are formed in excess and must remodel to achieve the precise synaptic connectivity characteristic of the mature... (Review)
Review
In the developing nervous system, synaptic connections are formed in excess and must remodel to achieve the precise synaptic connectivity characteristic of the mature organism. Synaptic pruning is a developmental process in which subsets of synapses are eliminated while the remaining synapses are preserved and strengthened. Recent findings have demonstrated unexpected roles for glial cells in this developmental process. These data demonstrate that phagocytic glia engulf synaptic and/or axonal elements in the developing nervous system and disruptions in this process result in sustained deficits in synaptic connectivity. These new findings highlight the importance of glia for nervous system development and function and may shed new light on mechanisms underlying nervous system disease.
Topics: Animals; Humans; Neurogenesis; Neuroglia; Phagocytes; Synapses
PubMed: 24157239
DOI: 10.1016/j.conb.2013.09.012 -
Experimental & Molecular Medicine May 2017The clearance of apoptotic cells is an essential process for tissue homeostasis. To this end, cells undergoing apoptosis must display engulfment signals, such as... (Review)
Review
The clearance of apoptotic cells is an essential process for tissue homeostasis. To this end, cells undergoing apoptosis must display engulfment signals, such as 'find-me' and 'eat-me' signals. Engulfment signals are recognized by multiple types of phagocytic machinery in phagocytes, leading to prompt clearance of apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic signals to reduce immune responses against apoptotic cell-derived self-antigens. Here we discuss recent advances in our knowledge of engulfment signals, the phagocytic machinery and the signal transduction pathways for apoptotic cell engulfment.
Topics: Animals; Apoptosis; Humans; Phagocytes; Phagocytosis; Signal Transduction
PubMed: 28496201
DOI: 10.1038/emm.2017.52 -
MBio Feb 2021Ingestion and killing of bacteria by phagocytic cells protect the human body against infections. While many mechanisms have been proposed to account for bacterial...
Ingestion and killing of bacteria by phagocytic cells protect the human body against infections. While many mechanisms have been proposed to account for bacterial killing in phagosomes, their relative importance, redundancy, and specificity remain unclear. In this study, we used the amoeba as a model phagocyte and quantified the requirement of 11 individual gene products, including nine putative effectors, for the killing of bacteria. This analysis revealed that radically different mechanisms are required to kill , , , , and AlyL, a lysozyme-like protein equipped with a distinct bacteriolytic region, plays a specific role in the intracellular killing of , with assistance from BpiC and Aoah, two lipopolysaccharide (LPS)-binding proteins. Rapid killing of and requires the presence of BpiC and of the NoxA NADPH oxidase. No single effector tested is essential for rapid killing of or Overall, our observations reveal an unsuspected degree of specificity in the elimination of bacteria in phagosomes. Phagocytic cells ingest and kill bacteria, a process essential for the defense of the human body against infections. Many potential killing mechanisms have been identified in phagocytic cells, including free radicals, toxic ions, enzymes, and permeabilizing peptides. Yet fundamental questions remain unanswered: what is the relative importance of these mechanisms, how redundant are they, and are different mechanisms used to kill different species of bacteria? We addressed these questions using , a model phagocytic cell amenable to genetic manipulations and quantitative analysis. Our results reveal that vastly different mechanisms are required to kill different species of bacteria. This very high degree of specificity was unexpected and indicates that a lot remains to be discovered about how phagocytic cells eliminate bacteria.
Topics: Bacteria; Dictyostelium; Klebsiella pneumoniae; Phagocytes; Phagocytosis; Phagosomes; Pseudomonas aeruginosa; Staphylococcus aureus
PubMed: 33593980
DOI: 10.1128/mBio.03169-20 -
Immunology Jul 2021Phagocytes form a family of immune cells that play a crucial role in tissue maintenance and help orchestrate the immune response. This family of cells can be separated... (Review)
Review
Phagocytes form a family of immune cells that play a crucial role in tissue maintenance and help orchestrate the immune response. This family of cells can be separated by their nuclear morphology into mononuclear and polymorphonuclear phagocytes. The generation of these cells in the bone marrow, to the blood and finally into tissues is a tightly regulated process. Ensuring the adequate production of these cells and their timely removal is key for both the initiation and resolution of inflammation. Insight into the kinetic profiles of innate myeloid cells during steady state and pathology will permit the rational development of therapies to boost the production of these cells in times of need or reduce them when detrimental.
Topics: Animals; Dendritic Cells; Homeostasis; Humans; Immunity, Innate; Inflammation; Macrophages; Monocytes; Mononuclear Phagocyte System; Neutrophils
PubMed: 33555612
DOI: 10.1111/imm.13320 -
Virulence Oct 2013The insect immune response demonstrates a number of structural and functional similarities to the innate immune system of mammals. As a result of these conserved... (Comparative Study)
Comparative Study Review
The insect immune response demonstrates a number of structural and functional similarities to the innate immune system of mammals. As a result of these conserved features insects have become popular choices for evaluating the virulence of microbial pathogens or for assessing the efficacy of antimicrobial agents and give results which are comparable to those that can be obtained using mammals. Analysis of the cellular component of the insect and mammalian immune systems demonstrates many similarities. Insect hemocytes recognize pathogens and phagocytose material in a similar manner to neutrophils. The killing of ingested microbes is achieved in both cell types by the production of superoxide and by the release of enzymes in the process of degranulation. Insect hemocytes and mammalian neutrophils are sensitive to the same inhibitors. This review highlights the strong similarities between the phagocytic cells of both groups of animals and demonstrates the potential benefits of using selected insects as in vivo screening systems.
Topics: Animals; Enzymes; Hemocytes; Insecta; Mammals; Phagocytes; Phagocytosis; Superoxides
PubMed: 23921374
DOI: 10.4161/viru.25906 -
PLoS Pathogens 2012
Review
Topics: Animals; Humans; Phagocytes; Toxoplasma; Toxoplasmosis
PubMed: 22876173
DOI: 10.1371/journal.ppat.1002794 -
The Netherlands Journal of Medicine Nov 2010Chronic granulomatous disease (CGD) was characterised half a century ago as a primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a... (Review)
Review
Chronic granulomatous disease (CGD) was characterised half a century ago as a primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a specific spectrum of bacteria and fungi and in concomitant hyperinflammation with widespread tissue granuloma formation. CGD now comprises five genetic defects, each impairing one of five essential subunits of the phagocyte NADPH oxidase generating reactive oxygen species. In the past few years CGD has lead to a new understanding of the importance of phagocyte oxygen metabolism for intra- and extracellular host defence and for resolution of the concomitant inflammatory process. In a not too distant future, this may help to tailor novel pharmacological and cellular interventions to the requirements of individual patients. This review covers recent advances in the pathophysiology of CGD and outlines today's clinical presentation as well as the basic principles for treatment of this relatively rare genetic disease. 'Fatal' granulomatous disease 50 years later has become a chronic inflammatory disorder with a median survival of 30 years and is of interest to both paediatricians and internists.
Topics: Genetic Counseling; Genetic Therapy; Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation; Humans; Inflammation; NADPH Oxidases; Phagocytes; Phagosomes; Reactive Oxygen Species; Recurrence
PubMed: 21116026
DOI: No ID Found -
Clinical Microbiology Reviews Oct 2000Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host... (Review)
Review
Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host defenses and various pathological settings characterized by excessive inflammation. Accordingly, they are key targets for immunomodulatory drugs, among which antibacterial agents are promising candidates. The basic and historical concepts of immunomodulation will first be briefly reviewed. Phagocyte complexity will then be unravelled (at least in terms of what we know about the origin, subsets, ambivalent roles, functional capacities, and transductional pathways of this cell and how to explore them). The core subject of this review will be the many possible interactions between antibacterial agents and phagocytes, classified according to demonstrated or potential clinical relevance (e.g., neutropenia, intracellular accumulation, and modulation of bacterial virulence). A detailed review of direct in vitro effects will be provided for the various antibacterial drug families, followed by a discussion of the clinical relevance of these effects in two particular settings: immune deficiency and inflammatory diseases. The prophylactic and therapeutic use of immunomodulatory antibiotics will be considered before conclusions are drawn about the emerging (optimistic) vision of future therapeutic prospects to deal with largely unknown new diseases and new pathogens by using new agents, new techniques, and a better understanding of the phagocyte in particular and the immune system in general.
Topics: Adjuvants, Immunologic; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Immunologic Factors; Phagocytes
PubMed: 11023961
DOI: 10.1128/CMR.13.4.615 -
Proceedings. Biological Sciences Jun 2018The digestive methods employed by amphioxus ()-both intracellular phagocytic digestion and extracellular digestion-have been discussed since 1937. Recent studies also...
The digestive methods employed by amphioxus ()-both intracellular phagocytic digestion and extracellular digestion-have been discussed since 1937. Recent studies also show that epithelial cells lining the digestive tract can express many immune genes. Here, in , using a special tissue fixation method, we show that some epithelial cells, especially those lining the large diverticulum protruding from the gut tube, phagocytize food particles directly, and can rely on this kind of phagocytic intracellular digestion to obtain energy throughout all stages of its life. Gene expression profiles suggest that diverticulum epithelial cells have functional features of both digestive cells and phagocytes. In starved , these cells accumulate endogenous digestive and hydrolytic enzymes, whereas, when sated, they express many kinds of immune genes in response to stimulation by phagocytized food particles. We also found that the distal hindgut epithelium can phagocytize food particles, but not as many. These results illustrate phagocytic intercellular digestion in , explain why digestive tract epithelial cells express typical immune genes and suggest that the main physiological function of the diverticulum is different from that of the vertebrate liver.
Topics: Animals; Digestion; Epithelial Cells; Gastrointestinal Tract; Lancelets; Phagocytes; Phagocytosis; Transcriptome
PubMed: 29875301
DOI: 10.1098/rspb.2018.0438 -
The Journal of Clinical Investigation Jan 2023
Topics: Phagocytes; Macrophages; Docosahexaenoic Acids; Receptors, G-Protein-Coupled
PubMed: 36647836
DOI: 10.1172/JCI168084