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MBio Dec 2019Macrophages are well known for their phagocytic activity and their role in innate immune responses. Macrophages eat non-self particles, via a variety of mechanisms, and... (Review)
Review
Macrophages are well known for their phagocytic activity and their role in innate immune responses. Macrophages eat non-self particles, via a variety of mechanisms, and typically break down internalized cargo into small macromolecules. However, some pathogenic agents have the ability to evade this endosomal degradation through a nonlytic exocytosis process termed vomocytosis. This phenomenon has been most often studied for , a yeast that causes roughly 180,000 deaths per year, primarily in immunocompromised (e.g., human immunodeficiency virus [HIV]) patients. Existing dogma purports that vomocytosis involves distinctive cellular pathways and intracellular physicochemical cues in the host cell during phagosomal maturation. Moreover, it has been observed that the immunological state of the individual and macrophage phenotype affect vomocytosis outcomes. Here we compile the current knowledge on the factors (with respect to the phagocytic cell) that promote vomocytosis of from macrophages.
Topics: Animals; Calcium; Cryptococcus neoformans; Humans; Hydrogen-Ion Concentration; Macrophages; Mice; Phagocytosis; Phagosomes; Phenotype
PubMed: 31874916
DOI: 10.1128/mBio.02526-19 -
Current Biology : CB Jul 2011
Topics: Humans; Phagocytosis; Phagosomes
PubMed: 21783028
DOI: 10.1016/j.cub.2011.05.053 -
Immunological Reviews Mar 2023Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating... (Review)
Review
Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating mechanisms is phagocytosis, the process of particle engulfment into a vacuole-like structure called the phagosome. The antimicrobial activity of the phagocytic process results from a collaboration of multiple systems and mechanisms within this organelle, where a complex interplay of ion fluxes, pH, reactive oxygen species, and antimicrobial proteins creates a dynamic antimicrobial environment. This complexity, combined with the difficulties of studying neutrophils ex vivo, has led to gaps in our knowledge of how the neutrophil phagosome optimizes pathogen killing. In particular, controversy has arisen regarding the relative contribution and integration of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived antimicrobial agents and granule-delivered antimicrobial proteins. Clinical syndromes arising from dysfunction in these systems in humans allow useful insight into these mechanisms, but their redundancy and synergy add to the complexity. In this article, we review the current knowledge regarding the formation and function of the neutrophil phagosome, examine new insights into the phagosomal environment that have been permitted by technological advances in recent years, and discuss aspects of the phagocytic process that are still under debate.
Topics: Humans; Neutrophils; Phagosomes; Phagocytosis; Phagocytes; Reactive Oxygen Species
PubMed: 36440666
DOI: 10.1111/imr.13173 -
Cell Sep 2011Genetic inhibition of autophagy induces degenerative changes in mammalian tissues that resemble those associated with aging, and normal and pathological aging are often... (Review)
Review
Genetic inhibition of autophagy induces degenerative changes in mammalian tissues that resemble those associated with aging, and normal and pathological aging are often associated with a reduced autophagic potential. Pharmacological or genetic manipulations that increase life span in model organisms often stimulate autophagy, and its inhibition compromises the longevity-promoting effects of caloric restriction, Sirtuin 1 activation, inhibition of insulin/insulin growth factor signaling, or the administration of rapamycin, resveratrol, or spermidine. Here, we discuss the probable cause and effect relationship between perturbed autophagy and aging, as well as possible molecular mechanisms that may mediate the anti-aging effects of autophagy.
Topics: Aging; Animals; Autophagy; Cell Death; Homeostasis; Humans; Mammals; Mitochondria; Phagosomes; Yeasts
PubMed: 21884931
DOI: 10.1016/j.cell.2011.07.030 -
Autophagy 2015
Topics: Animals; Autophagy; Humans; Lysosomes; Mitochondria; Neurons; Phagosomes
PubMed: 25831012
DOI: 10.1080/15548627.2015.1009790 -
The Journal of Cell Biology Jan 2018How do organelles coordinate their unique molecular identities between their cytosolic-facing surface membranes and their interior? In this issue, Naufer et al. (2017....
How do organelles coordinate their unique molecular identities between their cytosolic-facing surface membranes and their interior? In this issue, Naufer et al. (2017. https://doi.org/10.1083/jcb.201702179) discover an intriguing link between phagosome acidification and lipid signposts on their outer membrane.
Topics: Cell Membrane; Humans; Membrane Lipids; Organelles; Phagocytosis; Phagosomes
PubMed: 29233864
DOI: 10.1083/jcb.201711134 -
Frontiers in Immunology 2021Following phagocytosis, the nascent phagosome undergoes maturation to become a phagolysosome with an acidic, hydrolytic, and often oxidative lumen that can efficiently... (Review)
Review
Following phagocytosis, the nascent phagosome undergoes maturation to become a phagolysosome with an acidic, hydrolytic, and often oxidative lumen that can efficiently kill and digest engulfed microbes, cells, and debris. The fusion of phagosomes with lysosomes is a principal driver of phagosomal maturation and is targeted by several adapted intracellular pathogens. Impairment of this process has significant consequences for microbial infection, tissue inflammation, the onset of adaptive immunity, and disease. Given the importance of phagosome-lysosome fusion to phagocyte function and the many virulence factors that target it, it is unsurprising that multiple molecular pathways have evolved to mediate this essential process. While the full range of these pathways has yet to be fully characterized, several pathways involving proteins such as members of the Rab GTPases, tethering factors and SNAREs have been identified. Here, we summarize the current state of knowledge to clarify the ambiguities in the field and construct a more comprehensive phagolysosome formation model. Lastly, we discuss how other cellular pathways help support phagolysosome biogenesis and, consequently, phagocyte function.
Topics: Animals; Autophagy; Humans; Lysosomes; Membrane Fusion; Phagocytes; Phagocytosis; Phagosomes; SNARE Proteins; rab GTP-Binding Proteins
PubMed: 33717183
DOI: 10.3389/fimmu.2021.636078 -
Molecules and Cells Jan 2018Atg5 and Atg7 have long been considered as essential molecules for autophagy. However, we found that cells lacking these molecules still form autophagic vacuoles and... (Review)
Review
Atg5 and Atg7 have long been considered as essential molecules for autophagy. However, we found that cells lacking these molecules still form autophagic vacuoles and perform autophagic protein degradation when subjected to certain stressors. During this unconventional autophagy pathway, autophagosomes appeared to be generated in a Rab9-dependent manner by the fusion of vesicles derived from the -Golgi and late endosomes. Therefore, mammalian autophagy can occur via at least two different pathways; the Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Protein 5; Autophagy-Related Protein 7; Humans; Lysosomes; Microtubule-Associated Proteins; Models, Biological; Phagosomes
PubMed: 29370693
DOI: 10.14348/molcells.2018.2215 -
International Journal of Medical... Jan 2018Phagocytosis is essential for uptake and elimination of pathogenic microorganisms. Autophagy is a highly conserved mechanism for incorporation of cellular constituents... (Review)
Review
Phagocytosis is essential for uptake and elimination of pathogenic microorganisms. Autophagy is a highly conserved mechanism for incorporation of cellular constituents to replenish nutrients by degradation. Recently, parts of the autophagy machinery - above all microtubule-associated protein 1 light chain 3 (LC3) - were found to be specifically recruited to phagosomal membranes resulting in phagosome-lysosome fusion and efficient degradation of internalized cargo in a process termed LC3-associated phagocytosis (LAP). Many pathogenic bacterial, fungal and parasitic microorganisms reside within LAP-targeted single-membrane phagosomes or vacuoles after infection of host cells. In this minireview we describe the state of knowledge on the interaction of pathogens with LAP or LAP-like pathways and report on various pathogens that have evolved strategies to circumvent degradation in LAP compartments.
Topics: Animals; Bacteria; Fungi; Humans; Immune Evasion; Microtubule-Associated Proteins; Parasites; Phagocytosis; Phagosomes; Vacuoles
PubMed: 29169848
DOI: 10.1016/j.ijmm.2017.10.014 -
Virulence Dec 2019Autophagy is a conserved and fundamental cellular process mainly to recycle or eliminate dysfunctional cellular organelles or proteins. As a response to cellular stress,... (Review)
Review
Autophagy is a conserved and fundamental cellular process mainly to recycle or eliminate dysfunctional cellular organelles or proteins. As a response to cellular stress, autophagy is used as a defense mechanism to combat the infection with pathogenic bacteria. However, many intracellular bacteria have developed diverse mechanisms to evade recognition, to manipulate the autophagic pathway, and to hijack the autophagosomal compartment for replication. In this review, we discuss recent understandings on how bacteria interact with host autophagy.
Topics: Autophagy; Bacteria; Cytoplasm; Host-Pathogen Interactions; Humans; Lysosomes; Phagosomes
PubMed: 30978154
DOI: 10.1080/21505594.2019.1602020