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Cell Nov 2011Autophagy is the major intracellular degradation system by which cytoplasmic materials are delivered to and degraded in the lysosome. However, the purpose of autophagy... (Review)
Review
Autophagy is the major intracellular degradation system by which cytoplasmic materials are delivered to and degraded in the lysosome. However, the purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Here we provide a multidisciplinary review of our current understanding of autophagy's role in metabolic adaptation, intracellular quality control, and renovation during development and differentiation. We also explore how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease.
Topics: Animals; Autophagy; Disease Models, Animal; Humans; Mice; Neurodegenerative Diseases; Phagosomes; Plant Cells
PubMed: 22078875
DOI: 10.1016/j.cell.2011.10.026 -
Nature Jan 2011Autophagy is an essential, homeostatic process by which cells break down their own components. Perhaps the most primordial function of this lysosomal degradation pathway... (Review)
Review
Autophagy is an essential, homeostatic process by which cells break down their own components. Perhaps the most primordial function of this lysosomal degradation pathway is adaptation to nutrient deprivation. However, in complex multicellular organisms, the core molecular machinery of autophagy - the 'autophagy proteins' - orchestrates diverse aspects of cellular and organismal responses to other dangerous stimuli such as infection. Recent developments reveal a crucial role for the autophagy pathway and proteins in immunity and inflammation. They balance the beneficial and detrimental effects of immunity and inflammation, and thereby may protect against infectious, autoimmune and inflammatory diseases.
Topics: Animals; Autophagy; Cell Membrane; Humans; Immunity; Immunity, Innate; Infections; Inflammation; Phagosomes
PubMed: 21248839
DOI: 10.1038/nature09782 -
International Journal of Molecular... Jan 2019Epidemiological data from the Center of Disease Control (CDC) and the World Health Organization (WHO) statistics in 2017 show that 10.0 million people around the world... (Review)
Review
Epidemiological data from the Center of Disease Control (CDC) and the World Health Organization (WHO) statistics in 2017 show that 10.0 million people around the world became sick with tuberculosis. (MTB) is an intracellular parasite that mainly attacks macrophages and inhibits their apoptosis. It can become a long-term infection in humans, causing a series of pathological changes and clinical manifestations. In this review, we summarize innate immunity including the inhibition of antioxidants, the maturation and acidification of phagolysosomes and especially the apoptosis and autophagy of macrophages. Besides, we also elaborate on the adaptive immune response and the formation of granulomas. A thorough understanding of these escape mechanisms is of major importance for the prevention, diagnosis and treatment of tuberculosis.
Topics: Animals; Apoptosis; Autophagy; Humans; Immune Evasion; Mycobacterium tuberculosis; Oxidative Stress; Phagosomes
PubMed: 30650615
DOI: 10.3390/ijms20020340 -
Cell Feb 2010Autophagy has been implicated in many physiological and pathological processes. Accordingly, there is a growing scientific need to accurately identify, quantify, and...
Autophagy has been implicated in many physiological and pathological processes. Accordingly, there is a growing scientific need to accurately identify, quantify, and manipulate the process of autophagy. However, as autophagy involves dynamic and complicated processes, it is often analyzed incorrectly. In this Primer, we discuss methods to monitor autophagy and to modulate autophagic activity, with a primary focus on mammalian macroautophagy.
Topics: Animals; Autophagy; Cytological Techniques; Humans; Phagosomes
PubMed: 20144757
DOI: 10.1016/j.cell.2010.01.028 -
Immunological Reviews Mar 2015Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they... (Review)
Review
Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics.
Topics: Animals; Cell Communication; Host-Pathogen Interactions; Humans; Immunity, Innate; Lysosomes; Macrophage Activation; Macrophages; Metals; Mycobacterium tuberculosis; Phagocytes; Phagocytosis; Phagosomes; Tuberculosis
PubMed: 25703560
DOI: 10.1111/imr.12266 -
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 -
Current Biology : CB Jul 2011
Topics: Humans; Phagocytosis; Phagosomes
PubMed: 21783028
DOI: 10.1016/j.cub.2011.05.053 -
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 -
BioMed Research International 2017One hundred years have passed since the death of Élie Metchnikoff (1845-1916). He was the first to observe the uptake of particles by cells and realized the importance... (Review)
Review
One hundred years have passed since the death of Élie Metchnikoff (1845-1916). He was the first to observe the uptake of particles by cells and realized the importance of this process for the host response to injury and infection. He also was a strong advocate of the role of phagocytosis in cellular immunity, and with this he gave us the basis for our modern understanding of inflammation and the innate and acquired immune responses. Phagocytosis is an elegant but complex process for the ingestion and elimination of pathogens, but it is also important for the elimination of apoptotic cells and hence fundamental for tissue homeostasis. Phagocytosis can be divided into four main steps: (i) recognition of the target particle, (ii) signaling to activate the internalization machinery, (iii) phagosome formation, and (iv) phagolysosome maturation. In recent years, the use of new tools of molecular biology and microscopy has provided new insights into the cellular mechanisms of phagocytosis. In this review, we present a general view of our current knowledge on phagocytosis. We emphasize novel molecular findings, particularly on phagosome formation and maturation, and discuss aspects that remain incompletely understood.
Topics: Animals; Antigens; Humans; Phagocytosis; Phagosomes; Receptors, Immunologic; Signal Transduction
PubMed: 28691037
DOI: 10.1155/2017/9042851 -
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