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Cells Nov 2021Trogocytosis is a mode of internalization of a part of a live cell by nibbling and is mechanistically distinct from phagocytosis, which implies internalization of a... (Review)
Review
Trogocytosis is a mode of internalization of a part of a live cell by nibbling and is mechanistically distinct from phagocytosis, which implies internalization of a whole cell or a particle. Trogocytosis has been demonstrated in a broad range of cell types in multicellular organisms and is also known to be involved in a plethora of functions. In immune cells, trogocytosis is involved in the "cross-dressing" between antigen presenting cells and T cells, and is thus considered to mediate intercellular communication. On the other hand, trogocytosis has also been reported in a variety of unicellular organisms including the protistan (protozoan) parasite . ingests human T cell line by trogocytosis and acquires complement resistance and cross-dresses major histocompatibility complex (MHC) class I on the cell surface. Furthermore, trogocytosis and trogocytosis-like phenomena (nibbling of a live cell, not previously described as trogocytosis) have also been reported in other parasitic protists such as , , , and free-living amoebae. Thus, trogocytosis is conserved in diverse eukaryotic supergroups as a means of intercellular communication. It is depicting the universality of trogocytosis among eukaryotes. In this review, we summarize our current understanding of trogocytosis in unicellular organisms, including the history of its discovery, taxonomical distribution, roles, and molecular mechanisms.
Topics: Animals; Entamoeba histolytica; Eukaryota; Models, Biological; Parasites; Phagosomes; Trogocytosis
PubMed: 34831198
DOI: 10.3390/cells10112975 -
Biochemical Society Transactions Jun 2023Phagocytosis is an evolutionarily conserved important immunological process in higher organisms, and acts as the first line of defense against invading pathogenic... (Review)
Review
Phagocytosis is an evolutionarily conserved important immunological process in higher organisms, and acts as the first line of defense against invading pathogenic microbial infections. Additionally, this dynamic innate immune response is also critical for clearing apoptotic cells and/or tissues, is responsible for maintaining homeostasis and acts as a systemic regulator of critical physiological processes such as wound healing and tissue regeneration. Over the past two decades, numerous studies have shown that phagocytosis occurs in three spatiotemporally distinct steps, namely formation, maturation and resolution of the phagosome, and that, both the protein and lipid composition change as a function of the aforementioned steps during this immunological process. While significant knowledge is now available on the proteomic content of a phagosome during the different stages of phagocytosis, the lipidome however, remained lesser explored, until the past few years. In this review, we summarize recent efforts towards mapping the physiological roles and functions of three lipid classes, the phosphatidylinositols, cholesterol and sphingolipids during the various stages of phagocytosis, and discuss strategies evolved by microbes to hijack and/or disrupt these lipid pathways to evade the immune system. We conclude this review with some potential avenues that may be pursued towards mapping hitherto unknown lipid pathways during phagocytosis, and how this research might be beneficial in our ongoing battle to overcome pathogenic infections.
Topics: Proteomics; Phagocytosis; Phagosomes; Phosphatidylinositols; Immunity, Innate
PubMed: 37314030
DOI: 10.1042/BST20221424 -
Frontiers in Immunology 2022Non-tuberculous mycobacteria (NTM) are a heterogeneous group of originally environmental organi3sms, increasingly recognized as pathogens with rising prevalence... (Review)
Review
Non-tuberculous mycobacteria (NTM) are a heterogeneous group of originally environmental organi3sms, increasingly recognized as pathogens with rising prevalence worldwide. Knowledge of NTM's mechanisms of virulence is lacking, as molecular research of these bacteria is challenging, sometimes more than that of M. tuberculosis (Mtb), and far less resources are allocated to their investigation. While some of the virulence mechanisms are common to several mycobacteria including Mtb, others NTM species-specific. Among NTMs, Mycobacterium abscessus (Mabs) causes some of the most severe and difficult to treat infections, especially chronic pulmonary infections. Mabs survives and proliferates intracellularly by circumventing host defenses, using multiple mechanisms, many of which remain poorly characterized. Some of these immune-evasion mechanisms are also found in Mtb, including phagosome pore formation, inhibition of phagosome maturation, cytokine response interference and apoptosis delay. While much is known of the role of Mtb-secreted effector molecules in mediating the manipulation of the host response, far less is known of the secreted effector molecules in Mabs. In this review, we briefly summarize the knowledge of secreted effectors in Mtb (such as ESX secretion, SecA2, TAT and others), and draw the parallel pathways in Mabs. We also describe pathways that are unique to Mabs, differentiating it from Mtb. This review will assist researchers interested in virulence-associated secretion in Mabs by providing the knowledge base and framework for their studies.
Topics: Mycobacterium abscessus; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Phagosomes; Virulence
PubMed: 35880173
DOI: 10.3389/fimmu.2022.938895 -
Nature Chemical Biology Jun 2021Autophagy is implicated in a wide range of (patho)physiological processes including maintenance of cellular homeostasis, neurodegenerative disorders, aging and cancer.... (Review)
Review
Autophagy is implicated in a wide range of (patho)physiological processes including maintenance of cellular homeostasis, neurodegenerative disorders, aging and cancer. As such, small molecule autophagy modulators are in great demand, both for their ability to act as tools to better understand this essential process and as potential therapeutics. Despite substantial advances in the field, major challenges remain in the development and comprehensive characterization of probes that are specific to autophagy. In this Review, we discuss recent developments in autophagy-modulating small molecules, including the specific challenges faced in the development of activators and inhibitors, and recommend guidelines for their use. Finally, we discuss the potential to hijack the process for targeted protein degradation, an area of great importance in chemical biology and drug discovery.
Topics: Animals; Autophagy; Drug Discovery; Drug Therapy; Humans; Phagosomes; Small Molecule Libraries
PubMed: 34035513
DOI: 10.1038/s41589-021-00768-9 -
The FEBS Journal Mar 2021Phagocytosis is an essential mechanism for immunity and homeostasis, performed by a subset of cells known as phagocytes. Upon target engulfment, de novo formation of... (Review)
Review
Phagocytosis is an essential mechanism for immunity and homeostasis, performed by a subset of cells known as phagocytes. Upon target engulfment, de novo formation of specialized compartments termed phagosomes takes place. Phagosomes then undergo a series of fusion and fission events as they interact with the endolysosomal system and other organelles, in a dynamic process known as phagosome maturation. Because phagocytes play a key role in tissue patrolling and immune surveillance, phagosome maturation is associated with signaling pathways that link phagocytosis to antigen presentation and the development of adaptive immune responses. In addition, and depending on the nature of the cargo, phagosome integrity may be compromised, triggering additional cellular mechanisms including inflammation and autophagy. Upon completion of maturation, phagosomes enter a recently described phase: phagosome resolution, where catabolites from degraded cargo are metabolized, phagosomes are resorbed, and vesicles of phagosomal origin are recycled. Finally, phagocytes return to homeostasis and become ready for a new round of phagocytosis. Altogether, phagosome maturation and resolution encompass a series of dynamic events and organelle crosstalk that can be measured by biochemical, imaging, photoluminescence, cytometric, and immune-based assays that will be described in this guide.
Topics: Adaptive Immunity; Animals; Antigen Presentation; Autophagy; Endosomes; Humans; Immunity, Innate; Immunoassay; Immunologic Surveillance; Inflammation; Lysosomes; Molecular Probe Techniques; Phagocytes; Phagocytosis; Phagosomes; Signal Transduction
PubMed: 32757358
DOI: 10.1111/febs.15506 -
Methods in Molecular Biology (Clifton,... 2017Phagocytosis is the cellular internalization and sequestration of particulate matter into a `phagosome, which then matures into a phagolysosome. The phagolysosome then... (Review)
Review
Phagocytosis is the cellular internalization and sequestration of particulate matter into a `phagosome, which then matures into a phagolysosome. The phagolysosome then offers a specialized acidic and hydrolytic milieu that ultimately degrades the engulfed particle. In multicellular organisms, phagocytosis and phagosome maturation play two key physiological roles. First, phagocytic cells have an important function in tissue remodeling and homeostasis by eliminating apoptotic bodies, senescent cells and cell fragments. Second, phagocytosis is a critical weapon of the immune system, whereby cells like macrophages and neutrophils hunt and engulf a variety of pathogens and foreign particles. Not surprisingly, pathogens have evolved mechanisms to either block or alter phagocytosis and phagosome maturation, ultimately usurping the cellular machinery for their own survival. Here, we review past and recent discoveries that highlight how phagocytes recognize target particles, key signals that emanate after phagocyte-particle engagement, and how these signals help modulate actin-dependent remodeling of the plasma membrane that culminates in the release of the phagosome. We then explore processes related to early and late stages of phagosome maturation, which requires fusion with endosomes and lysosomes. We end this review by acknowledging that little is known about phagosome fission and even less is known about how phagosomes are resolved after particle digestion.
Topics: Animals; Cells; Endocytosis; Ligands; Phagocytosis; Phagosomes; Receptors, Cell Surface; Signal Transduction
PubMed: 27815869
DOI: 10.1007/978-1-4939-6581-6_1 -
Annual Review of Chemical and... Jun 2021When attempting to propagate infections, bacterial pathogens encounter phagocytes that encase them in vacuoles called phagosomes. Within phagosomes, bacteria are... (Review)
Review
When attempting to propagate infections, bacterial pathogens encounter phagocytes that encase them in vacuoles called phagosomes. Within phagosomes, bacteria are bombarded with a plethora of stresses that often lead to their demise. However, pathogens have evolved numerous strategies to counter those host defenses and facilitate survival. Given the importance of phagosome-bacteria interactions to infection outcomes, they represent a collection of targets that are of interest for next-generation antibacterials. To facilitate such therapies, different approaches can be employed to increase understanding of phagosome-bacteria interactions, and these can be classified broadly as top down (starting from intact systems and breaking down the importance of different parts) or bottom up (developing a knowledge base on simplified systems and progressively increasing complexity). Here we review knowledge of phagosomal compositions and bacterial survival tactics useful for bottom-up approaches, which are particularly relevant for the application of reaction engineering to quantify and predict the time evolution of biochemical species in these death-dealing vacuoles. Further, we highlight how understanding in this area can be built up through the combination of immunology, microbiology, and engineering.
Topics: Bacteria; Phagocytosis; Phagosomes
PubMed: 33781082
DOI: 10.1146/annurev-chembioeng-090920-015024 -
Cellular and Molecular Life Sciences :... Jul 2023During phagocytosis, endosomes both contribute with membrane to forming phagosomes and promote phagosome maturation. However, how these vesicles are delivered to the...
During phagocytosis, endosomes both contribute with membrane to forming phagosomes and promote phagosome maturation. However, how these vesicles are delivered to the phagocytic cup and the phagosome has been unknown. Here, we show that Protrudin-mediated endoplasmic reticulum (ER)-endosome contact sites facilitate anterograde translocation of FYCO1 and VAMP7-positive late endosomes and lysosomes (LELys) to forming phagocytic cups in a retinal pigment epithelial-derived cell line (RPE1). Protrudin-dependent phagocytic cup formation required SYT7, which promotes fusion of LELys with the plasma membrane. RPE1 cells perform phagocytosis of dead cells (efferocytosis) that expose phosphatidylserine (PS) on their surface. Exogenous addition of apoptotic bodies increased the formation of phagocytic cups, which further increased when Protrudin was overexpressed. Overexpression of Protrudin also led to elevated uptake of silica beads coated with PS. Conversely, Protrudin depletion or abrogation of ER-endosome contact sites inhibited phagocytic cup formation resulting in reduced uptake of PS-coated beads. Thus, the Protrudin pathway delivers endosomes to facilitate formation of the phagocytic cup important for PS-dependent phagocytosis.
Topics: Phagocytosis; Endoplasmic Reticulum; Lysosomes; Phagosomes; Endosomes
PubMed: 37468729
DOI: 10.1007/s00018-023-04862-0 -
The International Journal of... 2019The formation and processing of vesicles from the cell surface serves many important cellular functions ranging from nutrient acquisition to regulating the turnover of... (Review)
Review
The formation and processing of vesicles from the cell surface serves many important cellular functions ranging from nutrient acquisition to regulating the turnover of membrane components and signalling. In this article, we summarise the endocytic pathways of the social amoeba Dictyostelium from the clathrin-dependent and independent internalisation of surface components to the engulfment of bacteria or fluid by phagocytosis and macropinocytosis respectively. Due to similarities with the professional phagocytes of the mammalian immune system Dictyostelium has been extensively used to investigate the complex remodelling and trafficking events that occur as phagosomes and macropinosomes transit through the cell. Here we discuss what is known about this maturation process in order to kill any potential pathogens and obtain nutrients for growth. Finally, we aim to put these studies in evolutionary context and highlight some of the many questions that remain in our understanding of these complex and important pathways.
Topics: Cell Membrane; Cell Movement; Clathrin; Dictyostelium; Endocytosis; Exocytosis; Immune System; Lysosomes; Phagocytosis; Phagosomes; Pinocytosis; Signal Transduction
PubMed: 31840784
DOI: 10.1387/ijdb.190236jk -
Current Opinion in Microbiology Dec 2021Protozoa of the genus Leishmania are intracellular parasites that cause human leishmaniasis, a disease spread mostly in the tropics and subtropics. Leishmania cycle... (Review)
Review
Protozoa of the genus Leishmania are intracellular parasites that cause human leishmaniasis, a disease spread mostly in the tropics and subtropics. Leishmania cycle between the midgut of female sand flies and phagolysosome of mammalian macrophages. During their life cycle they constantly encounter changing nutritional environments. To monitor the external concentration of essential nutrients, the invading parasites employ sensors that report on the availability of these nutrients; but to-date only a few sensing pathways have been identified in Leishmania. This review focuses on the Arginine Deprivation Response, which both extracellular and intracellular Leishmania utilize to monitor environmental arginine and adjust their arginine transporter (AAP3) levels accordingly.
Topics: Animals; Arginine; Female; Humans; Leishmania; Leishmaniasis; Phagosomes; Psychodidae
PubMed: 34592588
DOI: 10.1016/j.mib.2021.09.003