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Cellular Microbiology Apr 2019Membrane bilayers of eukaryotic cells are an amalgam of lipids and proteins that distinguish organelles and compartmentalise cellular functions. The mammalian cell has... (Review)
Review
Membrane bilayers of eukaryotic cells are an amalgam of lipids and proteins that distinguish organelles and compartmentalise cellular functions. The mammalian cell has evolved mechanisms to sense membrane tension or damage and respond as needed. In the case of the plasma membrane and phagosomal membrane, these bilayers act as a barrier to microorganisms and are a conduit by which the host interacts with pathogens, including fungi such as Candida, Cryptococcus, Aspergillus, or Histoplasma species. Due to their size, morphological flexibility, ability to produce long filaments, secrete pathogenicity factors, and their potential to replicate within the phagosome, fungi can assault host membranes in a variety of physical and biochemical ways. In addition, the recent discovery of a fungal pore-forming peptide toxin further highlights the importance of membrane biology in the outcomes between host and fungal cells. In this review, we discuss the apparent "stretching" of membranes as a sophisticated biological response and the role of vesicular transport in combating membrane stress and damage. We also review the known pathogenicity factors and physical properties of fungal pathogens in the context of host membranes and discuss how this may contribute to pathogenic interactions between fungal and host cells.
Topics: Candida; Cell Membrane; Cryptococcus; Fungi; Phagosomes
PubMed: 30740852
DOI: 10.1111/cmi.13016 -
Journal of Leukocyte Biology Nov 2014Macrophages are capable of assuming distinct, meta-stable, functional phenotypes in response to environmental cues-a process referred to as macrophage polarization. The... (Review)
Review
Macrophages are capable of assuming distinct, meta-stable, functional phenotypes in response to environmental cues-a process referred to as macrophage polarization. The identity and plasticity of polarized macrophage subsets as well as their functions in the maintenance of homeostasis and the progression of various pathologies have become areas of intense interest. Yet, the mechanisms by which they achieve subset-specific functions at the cellular level remain unclear. It is becoming apparent that phagocytosis and phagosome maturation differ depending on the polarization of macrophages. This minireview summarizes recent progress in this field, highlighting developing trends and discussing the molecular mechanisms that underlie subset-specific functions.
Topics: Animals; Cell Polarity; Host-Pathogen Interactions; Humans; Hydrogen-Ion Concentration; Macrophages; Phagocytosis; Phagosomes
PubMed: 24868088
DOI: 10.1189/jlb.1MR0114-021R -
Microbes and Infection Oct 2016Rab GTPases' subversion by intracellular pathogens during infection has been extensively documented. Recent findings have implicated a key intracellular bacterial... (Review)
Review
Rab GTPases' subversion by intracellular pathogens during infection has been extensively documented. Recent findings have implicated a key intracellular bacterial restriction/containment function for Rab32/38 in Salmonella species in macrophages and Listeria monocytogenes in dendritic cells. Rab32/38 aids the phagolysosome maturation, and mediates a parallel xenophagy mechanism by engaging prohibitins.
Topics: Dendritic Cells; Humans; Listeria monocytogenes; Lysosomes; Macrophages; Phagosomes; Salmonella; rab GTP-Binding Proteins
PubMed: 27256464
DOI: 10.1016/j.micinf.2016.05.006 -
Biochimica Et Biophysica Acta.... Sep 2017Phagocytosis is an essential mechanism through which innate immune cells ingest foreign material that is either destroyed or used to generate and present antigens and... (Review)
Review
Phagocytosis is an essential mechanism through which innate immune cells ingest foreign material that is either destroyed or used to generate and present antigens and initiate adaptive immune responses. While a role for the ER during phagosome biogenesis has been recognized, whether fusion with ER cisternae or vesicular derivatives occurs has been the source of much contention. Membrane contact sites (MCS) are tight appositions between ER membranes and various organelles that coordinate multiple functions including localized signalling, lipid transfer and trafficking. The discovery that MCS form between the ER and phagosomes now begs the question of whether MCS play a role in connecting the ER to phagosomes under different contexts. In this review, we consider the implications of MCS between the ER and phagosomes during cross-presentation and infection with intracellular pathogens. We also discuss the similarities between these contacts and those between the ER and plasma membrane and acidic organelles such as endosomes and lysosomes. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.
Topics: Animals; Calcium Signaling; Endoplasmic Reticulum; Humans; Membrane Fusion; Phagosomes
PubMed: 28432021
DOI: 10.1016/j.bbamcr.2017.04.007 -
Nature Chemical Biology Mar 2019
Topics: DNA; Freedom; Movement; Phagosomes
PubMed: 30664684
DOI: 10.1038/s41589-019-0224-7 -
Emerging Microbes & Infections Dec 2024The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of (Mtb) are necessary to identify...
The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbĪ± which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.
Topics: Animals; Humans; Mice; Interleukin-16; Macrophages; Mycobacterium tuberculosis; Phagosomes; Tuberculosis; Zebrafish
PubMed: 38380651
DOI: 10.1080/22221751.2024.2322663 -
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 -
Advances in Experimental Medicine and... 2020The formation and maturation of phagosomes are accompanied by acute changes in lipid metabolism. Phosphoinositides, in particular, undergo extensive modification as part... (Review)
Review
The formation and maturation of phagosomes are accompanied by acute changes in lipid metabolism. Phosphoinositides, in particular, undergo extensive modification as part of the signaling sequence that drives cytoskeletal and membrane remodeling. Because the phosphoinositides provide much of the anionic charge of the cytosolic leaflet of the plasmalemma and phagosomal membrane, the metabolic changes associated with signaling result in marked changes of the surface charge. Here we summarize the pathways involved in lipid remodeling during phagocytosis, the resultant alterations in the surface charge of the nascent and maturing phagosomes, and the consequent effects on the association of proteins attached to the membrane by electrostatic means.
Topics: Cell Membrane; Intracellular Membranes; Phagocytosis; Phagosomes; Signal Transduction
PubMed: 32399824
DOI: 10.1007/978-3-030-40406-2_3 -
Genes Jan 2023is the enteric protozoan parasite responsible for amebiasis. Trophozoites of ingest human cells in the intestine and other organs, which is the hallmark of its... (Review)
Review
is the enteric protozoan parasite responsible for amebiasis. Trophozoites of ingest human cells in the intestine and other organs, which is the hallmark of its pathogenesis. Phagocytosis and trogocytosis are pivotal biological functions for its virulence and also contribute to the proliferation of nutrient uptake from the environment. We previously elucidated the role of a variety of proteins associated with phagocytosis and trogocytosis, including Rab small GTPases, Rab effectors, including retromer, phosphoinositide-binding proteins, lysosomal hydrolase receptors, protein kinases, and cytoskeletal proteins. However, a number of proteins involved in phagocytosis and trogocytosis remain to be identified, and mechanistic details of their involvement must be elucidated at the molecular level. To date, a number of studies in which a repertoire of proteins associated with phagosomes and potentially involved in phagocytosis have been conducted. In this review, we revisited all phagosome proteome studies we previously conducted in order to reiterate information on the proteome of phagosomes. We demonstrated the core set of constitutive phagosomal proteins and also the set of phagosomal proteins recruited only transiently or in condition-dependent fashions. The catalogs of phagosome proteomes resulting from such analyses can be a useful source of information for future mechanistic studies as well as for confirming or excluding a possibility of whether a protein of interest in various investigations is likely or is potentially involved in phagocytosis and phagosome biogenesis.
Topics: Humans; Entamoeba histolytica; Proteome; Proteomics; Phagocytosis; Phagosomes; rab GTP-Binding Proteins
PubMed: 36833306
DOI: 10.3390/genes14020379 -
Cellular Microbiology Mar 2015Salmonellae have the ability to invade, persist and replicate within an intracellular phagosome termed the Salmonella-containing vacuole (SCV). Salmonellae alter lipid... (Review)
Review
Salmonellae have the ability to invade, persist and replicate within an intracellular phagosome termed the Salmonella-containing vacuole (SCV). Salmonellae alter lipid and protein content of the SCV membrane and manipulate cytoskeletal elements in contact with the SCV using the Salmonella pathogenicity island 1 (SPI-2) type III secretion system effectors. These modifications result in microtubular-based movement and morphological changes, which include endosomal tubulation of the SCV membrane. SseJ is a SPI-2 effector that localizes to the cytoplasmic face of the SCV and esterifies cholesterol through its glycerophospholipid : cholesterol acyltransferase activity. SseJ enzymatic activity as well as localization to the SCV are determined by binding to the small mammalian GTPase, RhoA. This review will focus on current knowledge about the role of SseJ in SCV membrane modification and will discuss how the hypothesis that a major role of SPI-2 effectors is to modify SCV protein and lipid content to promote bacterial intracellular survival.
Topics: Acyltransferases; Host-Pathogen Interactions; Intracellular Membranes; Phagosomes; Phospholipids; Protein Binding; Salmonella; Virulence Factors; rhoA GTP-Binding Protein
PubMed: 25620407
DOI: 10.1111/cmi.12420