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Glycobiology Sep 2013A growing list of innate immune receptors is being defined that recognize polysaccharides of microbial cell walls. Fungal β-glucan recognition by the receptor Dectin-1... (Review)
Review
A growing list of innate immune receptors is being defined that recognize polysaccharides of microbial cell walls. Fungal β-glucan recognition by the receptor Dectin-1 triggers inflammatory immune responses in macrophages and dendritic cells that are appropriate for defense against fungal pathogens. Among these responses is the specific recruitment of the autophagy-related protein light chain 3 (LC3) to phagosomes containing fungi. Studies documenting LC3's recruitment to phagosomes containing β-glucan and other nonsugar particles suggest that LC3 plays a role in regulating phagocytosis and its related immunological responses.
Topics: Animals; Autophagy; Humans; Lectins, C-Type; Phagocytosis; Phagosomes; Signal Transduction; beta-Glucans
PubMed: 23749474
DOI: 10.1093/glycob/cwt046 -
Frontiers in Cellular and Infection... 2014Internalization and degradation of live Bb within phagosomal compartments of monocytes, macrophages and dendritic cells (DCs), allows for the release of lipoproteins,... (Review)
Review
Internalization and degradation of live Bb within phagosomal compartments of monocytes, macrophages and dendritic cells (DCs), allows for the release of lipoproteins, nucleic acids and other microbial products, triggering a broad and robust inflammatory response. Toll-like receptors (TLRs) are key players in the recognition of spirochetal ligands from whole viable organisms (i.e., vita-PAMPs). Herein we will review the role of endosomal TLRs in the response to the Lyme disease spirochete.
Topics: Animals; Borrelia burgdorferi; Humans; Lyme Disease; Phagocytes; Phagosomes; Signal Transduction; Toll-Like Receptors
PubMed: 24904837
DOI: 10.3389/fcimb.2014.00055 -
Autophagy Feb 2021Macroautophagy/autophagy is a complex process that involves over 40 proteins in . How these proteins are organized, and their activities orchestrated to facilitate an...
Macroautophagy/autophagy is a complex process that involves over 40 proteins in . How these proteins are organized, and their activities orchestrated to facilitate an efficient autophagic mechanism remain elusive. Sawa-Makarsha et al. reconstitute the initial steps of autophagosome biogenesis during selective autophagy using autophagy factors purified from yeast. Their results show that Atg9 vesicles serve as platforms for the recruitment of the autophagy machinery, and establish membrane contact sites to initiate lipid transfer for autophagosome biogenesis.: GUV, giant unilamellar vesicles; PAS, phagophore assembly site; PL, proteolipisomes.
Topics: Autophagosomes; Autophagy; Autophagy-Related Proteins; Membrane Proteins; Phagosomes; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 33092448
DOI: 10.1080/15548627.2020.1835231 -
Biochimica Et Biophysica Acta.... Jun 2021The emergence of endo-lysosomes as ubiquitous Ca stores with their unique cohort of channels has resulted in their being implicated in a growing number of processes in... (Review)
Review
The emergence of endo-lysosomes as ubiquitous Ca stores with their unique cohort of channels has resulted in their being implicated in a growing number of processes in an ever-increasing number of cell types. The architectural and regulatory constraints of these acidic Ca stores distinguishes them from other larger Ca sources such as the ER and influx across the plasma membrane. In view of recent advances in the understanding of the modes of operation, we discuss phagocytosis as a template for how endo-lysosomal Ca signals (generated via TPC and TRPML channels) can be integrated in multiple sophisticated ways into biological processes. Phagocytosis illustrates how different endo-lysosomal Ca signals drive different phases of a process, and how these can be altered by disease or infection.
Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Cell Membrane; Endosomes; Humans; Lysosomes; NADP; Phagocytosis; Phagosomes; Transient Receptor Potential Channels
PubMed: 33872669
DOI: 10.1016/j.bbamcr.2021.119040 -
Microbiology Spectrum Oct 2014Through thousands of years of reciprocal coevolution, Mycobacterium tuberculosis has become one of humanity's most successful pathogens, acquiring the ability to... (Review)
Review
Through thousands of years of reciprocal coevolution, Mycobacterium tuberculosis has become one of humanity's most successful pathogens, acquiring the ability to establish latent or progressive infection and persist even in the presence of a fully functioning immune system. The ability of M. tuberculosis to avoid immune-mediated clearance is likely to reflect a highly evolved and coordinated program of immune evasion strategies that interfere with both innate and adaptive immunity. These include the manipulation of their phagosomal environment within host macrophages, the selective avoidance or engagement of pattern recognition receptors, modulation of host cytokine production, and the manipulation of antigen presentation to prevent or alter the quality of T-cell responses. In this article we review an extensive array of published studies that have begun to unravel the sophisticated program of specific mechanisms that enable M. tuberculosis and other pathogenic mycobacteria to persist and replicate in the face of considerable immunological pressure from their hosts. Unraveling the mechanisms by which M. tuberculosis evades or modulates host immune function is likely to be of major importance for the development of more effective new vaccines and targeted immunotherapy against tuberculosis.
Topics: Adaptive Immunity; Animals; Host-Pathogen Interactions; Humans; Immune Evasion; Immunity, Innate; Macrophages; Mycobacterium tuberculosis; Phagosomes
PubMed: 26104343
DOI: 10.1128/microbiolspec.MGM2-0005-2013 -
Current Opinion in Immunology Feb 2014A decade of work shows that the core function of phagocytosis in engulfment and destruction of microorganisms is only a small facet of the full spectrum of roles for... (Review)
Review
A decade of work shows that the core function of phagocytosis in engulfment and destruction of microorganisms is only a small facet of the full spectrum of roles for phagocytosis in the immune system. The regulation of phagocytosis and its outcomes by inflammatory pattern recognition receptors (PRRs) is now followed by new studies strengthening this concept and adding further complexity to the relationship between phagocytosis and innate immune signaling. Phagocytosis forms the platform for activation of distinct members of the Toll-like receptor family, and even dictates their signaling outcomes. In many cases, phagocytosis is a necessary precedent to the activation of cytosolic PRRs and assembly of canonical and non-canonical inflammasomes, leading to strong pro-inflammatory responses and inflammatory cell death.
Topics: Animals; Cell Death; Cytosol; Endosomes; Humans; Immunity, Innate; Inflammasomes; Nucleic Acids; Phagocytes; Phagocytosis; Phagosomes; Receptors, Pattern Recognition; Signal Transduction
PubMed: 24556406
DOI: 10.1016/j.coi.2013.11.003 -
Current Biology : CB Apr 2018Macroautophagy is a conserved intracellular lysosomal degradative pathway, vital for the maintenance of cellular homeostasis. It is characterized by double-membrane... (Review)
Review
Macroautophagy is a conserved intracellular lysosomal degradative pathway, vital for the maintenance of cellular homeostasis. It is characterized by double-membrane vesicles called autophagosomes, which sequester the cytoplasmic material destined for lysosomal turnover. In a final step, autophagosomes fuse with lysosomes to release their cargo into the acidic and hydrolytic lumen of these organelles. In recent years, numerous new insights into this fusion event have been gained. Notably, many proteins implicated in autophagosome-lysosome fusion interact with members of the Atg8 protein family. Moreover, Atg8 proteins are described to have intrinsic membrane tethering and fusogenic properties themselves. Here, we summarize the current knowledge about the members of this intriguing protein family, which highlights them as possible hubs for the coordination of the final fusion stages of autophagy.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Protein 8 Family; Cytosol; Humans; Lysosomes; Membrane Fusion; Phagosomes
PubMed: 29689234
DOI: 10.1016/j.cub.2018.02.034 -
Physiological Reviews Oct 2010(Macro)autophagy is a bulk degradation process that mediates the clearance of long-lived proteins and organelles. Autophagy is initiated by double-membraned structures,... (Review)
Review
(Macro)autophagy is a bulk degradation process that mediates the clearance of long-lived proteins and organelles. Autophagy is initiated by double-membraned structures, which engulf portions of cytoplasm. The resulting autophagosomes ultimately fuse with lysosomes, where their contents are degraded. Although the term autophagy was first used in 1963, the field has witnessed dramatic growth in the last 5 years, partly as a consequence of the discovery of key components of its cellular machinery. In this review we focus on mammalian autophagy, and we give an overview of the understanding of its machinery and the signaling cascades that regulate it. As recent studies have also shown that autophagy is critical in a range of normal human physiological processes, and defective autophagy is associated with diverse diseases, including neurodegeneration, lysosomal storage diseases, cancers, and Crohn's disease, we discuss the roles of autophagy in health and disease, while trying to critically evaluate if the coincidence between autophagy and these conditions is causal or an epiphenomenon. Finally, we consider the possibility of autophagy upregulation as a therapeutic approach for various conditions.
Topics: Animals; Autophagy; Eukaryotic Cells; Humans; Mammals; Phagosomes; Signal Transduction; Stress, Physiological
PubMed: 20959619
DOI: 10.1152/physrev.00030.2009 -
Seminars in Immunology Mar 2023Dendritic cells (DCs) present internalized antigens to CD8 T cells through cross-presentation by major histocompatibility complex class I (MHC-I) molecules. While... (Review)
Review
Dendritic cells (DCs) present internalized antigens to CD8 T cells through cross-presentation by major histocompatibility complex class I (MHC-I) molecules. While conventional cDC1 excel at cross-presentation, cDC2 can be licensed to cross-present during infection by signals from inflammatory receptors, most prominently Toll-like receptors (TLRs). At the core of the regulation of cross-presentation by TLRs is the control of subcellular MHC-I traffic. Within DCs, MHC-I are enriched within endosomal recycling compartments (ERC) and traffic to microbe-carrying phagosomes under the control of phagosome-compartmentalized TLR signals to favor CD8 T cell cross-priming to microbial antigens. Viral blockade of the transporter associated with antigen processing (TAP), known to inhibit the classic MHC-I presentation of cytoplasmic protein-derived peptides, depletes the ERC stores of MHC-I to simultaneously also block TLR-regulated cross-presentation. DCs counter this impairment in the two major pathways of MHC-I presentation to CD8 T cells by mobilizing noncanonical cross-presentation, which delivers MHC-I to phagosomes from a new location in the ER-Golgi intermediate compartment (ERGIC) where MHC-I abnormally accumulate upon TAP blockade. Noncanonical cross-presentation thus rescues MHC-I presentation and cross-primes TAP-independent CD8 T cells best-matched against target cells infected with immune evasive viruses. Because noncanonical cross-presentation relies on a phagosome delivery route of MHC-I that is not under TLR control, it risks potential cross-presentation of self-antigens during infection. Here I review these findings to illustrate how the subcellular route of MHC-I to phagosomes critically impacts the regulation of cross-presentation and the nature of the CD8 T cell response to infection and cancer. I highlight important and novel implications to CD8 T cell vaccines and immunotherapy.
Topics: Humans; Dendritic Cells; Histocompatibility Antigens Class I; CD8-Positive T-Lymphocytes; Antigen Presentation; Phagosomes; Antigens; Toll-Like Receptors; HLA Antigens
PubMed: 36706521
DOI: 10.1016/j.smim.2023.101713 -
ELife Mar 2023neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a...
neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that exophers produced by mechanosensory neurons in are engulfed by surrounding hypodermal skin cells and are then broken up into numerous smaller vesicles that acquire hypodermal phagosome maturation markers, with vesicular contents gradually degraded by hypodermal lysosomes. Consistent with the hypodermis acting as an exopher phagocyte, we found that exopher removal requires hypodermal actin and Arp2/3, and the hypodermal plasma membrane adjacent to newly formed exophers accumulates dynamic F-actin during budding. Efficient fission of engulfed exopher-phagosomes to produce smaller vesicles and degrade their contents requires phagosome maturation factors SAND-1/Mon1, GTPase RAB-35, the CNT-1 ARF-GAP, and microtubule motor-associated GTPase ARL-8, suggesting a close coupling of phagosome fission and phagosome maturation. Lysosome activity was required to degrade exopher contents in the hypodermis but not for exopher-phagosome resolution into smaller vesicles. Importantly, we found that GTPase ARF-6 and effector SEC-10/exocyst activity in the hypodermis, along with the CED-1 phagocytic receptor, is required for efficient production of exophers by the neuron. Our results indicate that the neuron requires specific interaction with the phagocyte for an efficient exopher response, a mechanistic feature potentially conserved with mammalian exophergenesis, and similar to neuronal pruning by phagocytic glia that influences neurodegenerative disease.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Neurodegenerative Diseases; Apoptosis; Phagocytosis; Phagosomes; Neurons; Neuroglia; Carrier Proteins; GTP Phosphohydrolases; Mammals
PubMed: 36861960
DOI: 10.7554/eLife.82227