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Brain : a Journal of Neurology Aug 2022Glial cell activation is a hallmark of several neurodegenerative and neuroinflammatory diseases. During HIV infection, neuroinflammation is associated with cognitive...
Glial cell activation is a hallmark of several neurodegenerative and neuroinflammatory diseases. During HIV infection, neuroinflammation is associated with cognitive impairment, even during sustained long-term suppressive antiretroviral therapy. However, the cellular subsets contributing to neuronal damage in the CNS during HIV infection remain unclear. Using post-mortem brain samples from eight HIV patients and eight non-neurological disease controls, we identify a subset of CNS phagocytes highly enriched in LGALS3, CTSB, GPNMB and HLA-DR, a signature identified in the context of ageing and neurodegeneration. In HIV patients, the presence of this phagocyte phenotype was associated with synaptic stripping, suggesting an involvement in the pathogenesis of HIV-associated neurocognitive disorder. Taken together, our findings elucidate some of the molecular signatures adopted by CNS phagocytes in HIV-positive patients and contribute to the understanding of how HIV might pave the way to other forms of cognitive decline in ageing HIV patient populations.
Topics: Brain; HIV Infections; Humans; Membrane Glycoproteins; Neurocognitive Disorders; Neurons; Phagocytes; Synapses
PubMed: 35808999
DOI: 10.1093/brain/awac102 -
Frontiers in Immunology 2019The clearance of apoptotic cells is pivotal for both maintaining tissue homeostasis and returning to homeostasis after tissue injury as part of the regenerative... (Review)
Review
The clearance of apoptotic cells is pivotal for both maintaining tissue homeostasis and returning to homeostasis after tissue injury as part of the regenerative resolution response. The liver is known for its capacity to remove aged and damaged cells from the circulation and can serve as a graveyard for effector T cells. In particular Kupffer cells are active phagocytic cells, but during hepatic inflammatory responses incoming neutrophils and monocytes may contribute to pro-inflammatory damage. To stimulate resolution of such inflammation, myeloid cell function can change, via sensing of environmental changes in the inflammatory milieu. Also, the removal of apoptotic cells via efferocytosis and the signaling pathways that are activated in macrophages/phagocytes upon their engulfment of apoptotic cells are important for a return to tissue homeostasis. Here, we will discuss, how efferocytosis mechanisms in hepatic macrophages/phagocytes may regulate tissue homeostasis and be involved in tissue regeneration in liver disease.
Topics: Animals; Homeostasis; Humans; Liver; Liver Diseases; Macrophages; Phagocytosis
PubMed: 31798592
DOI: 10.3389/fimmu.2019.02670 -
Biochemical Society Transactions Apr 2021Although millions of cells in the human body will undergo programmed cell death each day, dying cells are rarely detected under homeostatic settings in vivo. The swift... (Review)
Review
Although millions of cells in the human body will undergo programmed cell death each day, dying cells are rarely detected under homeostatic settings in vivo. The swift removal of dying cells is due to the rapid recruitment of phagocytes to the site of cell death which then recognise and engulf the dying cell. Apoptotic cell clearance - the engulfment of apoptotic cells by phagocytes - is a well-defined process governed by a series of molecular factors including 'find-me', 'eat-me', 'don't eat-me' and 'good-bye' signals. However, in recent years with the rapid expansion of the cell death field, the removal of other necrotic-like cell types has drawn much attention. Depending on the type of death, dying cells employ different mechanisms to facilitate engulfment and elicit varying functional impacts on the phagocyte, from wound healing responses to inflammatory cytokine secretion. Nevertheless, despite the mechanism of death, the clearance of dying cells is a fundamental process required to prevent the uncontrolled release of pro-inflammatory mediators and inflammatory disease. This mini-review summarises the current understandings of: (i) apoptotic, necrotic, necroptotic and pyroptotic cell clearance; (ii) the functional consequences of dying cell engulfment and; (iii) the outstanding questions in the field.
Topics: Animals; Apoptosis; Cytokines; Humans; Models, Biological; Necroptosis; Necrosis; Phagocytes; Phagocytosis; Pyroptosis; Signal Transduction
PubMed: 33843978
DOI: 10.1042/BST20200696 -
Journal of Neuroinflammation Nov 2023Traumatic spinal cord injury can cause immediate physical damage to the spinal cord and result in severe neurological deficits. The primary, mechanical tissue damage...
Traumatic spinal cord injury can cause immediate physical damage to the spinal cord and result in severe neurological deficits. The primary, mechanical tissue damage triggers a variety of secondary damage mechanisms at the injury site which significantly contribute to a larger lesion size and increased functional damage. Inflammatory mechanisms which directly involve both microglia (MG) and monocyte-derived macrophages (MDM) play important roles in the post-injury processes, including inflammation and debris clearing. In the current study, we investigated changes in the structure and function of MG/MDM in the injured spinal cord of adult female mice, 7 days after a thoracic contusion SCI. With the use of chip mapping scanning electron microscopy, which allows to image large samples at the nanoscale, we performed an ultrastructural comparison of MG/MDM located near the lesion vs adjacent regions to provide novel insights into the mechanisms at play post-injury. We found that MG/MDM located near the lesion had more mitochondria overall, including mitochondria with and without morphological alterations, and had a higher proportion of altered mitochondria. MG/MDM near the lesion also showed an increased number of phagosomes, including phagosomes containing myelin and partiallydigested materials. MG/MDM near the injury interacted differently with the spinal cord parenchyma, as shown by their reduced number of direct contacts with synaptic elements, axon terminals and dendritic spines. In this study, we characterized the ultrastructural changes of MG/MDM in response to spinal cord tissue damage in mice, uncovering changes in phagocytic activity, mitochondrial ultrastructure, and inter-cellular interactions within the spinal cord parenchyma.
Topics: Mice; Female; Animals; Microglia; Macrophages; Spinal Cord Injuries; Phagocytes; Spinal Cord
PubMed: 37990235
DOI: 10.1186/s12974-023-02953-0 -
Frontiers in Immunology 2019Mononuclear phagocytes are antigen presenting cells that play a key role in linking the innate and adaptive immune systems. In tissue, these consist of Langerhans cells,... (Review)
Review
Mononuclear phagocytes are antigen presenting cells that play a key role in linking the innate and adaptive immune systems. In tissue, these consist of Langerhans cells, dendritic cells and macrophages, all of which express the key HIV entry receptors CD4 and CCR5 making them directly infectible with HIV. Mononuclear phagocytes are the first cells of the immune system to interact with invading pathogens such as HIV. Each cell type expresses a specific repertoire of pathogen binding receptors which triggers pathogen uptake and the release of innate immune cytokines. Langerhans cells and dendritic cells migrate to lymph nodes and present antigens to CD4 T cells, whereas macrophages remain tissue resident. Here we review how HIV-1 manipulates these cells by blocking their ability to produce innate immune cytokines and taking advantage of their antigen presenting cell function in order to gain transport to its primary target cells, CD4 T cells.
Topics: CD4 Antigens; CD4-Positive T-Lymphocytes; Dendritic Cells; HIV Infections; HIV-1; Humans; Langerhans Cells; Macrophages; Phagocytes; Receptors, CCR5
PubMed: 31616434
DOI: 10.3389/fimmu.2019.02263 -
Journal of Gynecology Obstetrics and... Apr 2021Endometriosis is a chronic systemic disease, which influence negatively the quality of life of affected women and responsible for infertility and chronic pelvic pain....
INTRODUCTION
Endometriosis is a chronic systemic disease, which influence negatively the quality of life of affected women and responsible for infertility and chronic pelvic pain. Pathophysiology of the disease is still enigmatic, but insufficient immune surveillance may play a role in it. Peripheral natural immune cell function is rarely examined. The aim of the study was to examine phagocyte function of peripheral neutrophil granulocytes and monocytes, whether this phagocytic activity is affected by the presence or removal of endometriotic lesions in women with endometriosis.
MATERIAL AND METHODS
Twenty-six preoperative, 13 postoperative samples from women with endometriosis, 23 samples from healthy women, 14 pre- and postoperative samples from the surgical control group were enrolled. Cells were isolated from peripheral blood samples, marked and evaluated for the phagocytosis index with immunofluorescent microscope after phagocyting the zymosane molecules.
RESULTS
Phagocyte function of monocytes and neutrophil granulocytes decreased significantly women with endometriosis before surgery compared to healthy controls. However, 7 days after surgery the postoperative values showed significant improvement compared to the preoperative results of women with endometriosis. This increment reached the values of the healthy women. In the surgical control group no difference was detected between the pre- and postoperative outcomes.
DISCUSSION
Decreased phagocyte function of the examined cells, which can be the result of the circulating immunosuppressive factors, may play a role in the deficient clearance of ectopic endometrial tissue. Based on the postoperative results, these immunosuppressive factors may be reduced or eliminated 7 days after surgery in women with endometriosis.
Topics: Case-Control Studies; Endometriosis; Female; Granulocytes; Humans; Immunity, Cellular; Monocytes; Neutrophils; Phagocytosis; Postoperative Period
PubMed: 32413524
DOI: 10.1016/j.jogoh.2020.101796 -
Journal of Advanced Research Jul 2021Even though exosome-based therapy has been shown to be able to control the progression of different pathologies, the data revealed by pharmacokinetic studies warn of the... (Review)
Review
BACKGROUND
Even though exosome-based therapy has been shown to be able to control the progression of different pathologies, the data revealed by pharmacokinetic studies warn of the low residence time of exogenous exosomes in circulation that can hinder the clinical translation of therapeutic exosomes. The macrophages related to the organs of the mononuclear phagocytic system are responsible primarily for the rapid clearance and retention of exosomes, which strongly limits the amount of exosomal particles available to reach the target tissue, accumulate in it and release with high efficiency its therapeutic cargo in acceptor target cells to exert the desired biological effect.
AIM OF REVIEW
Endowing exosomes with surface modifications to evade the immune system is a plausible strategy to contribute to the suppression of exosomal clearance and increase the efficiency of their targeted content delivery. Here, we summarize the current evidence about the mechanisms underlying the recognition and sequestration of therapeutic exosomes by phagocytic cells. Also, we propose different strategies to generate 'invisible' exosomes for the immune system, through the incorporation of different anti-phagocytic molecules on the exosomes' surface that allow increasing the circulating half-life of therapeutic exosomes with the purpose to increase their bioavailability to reach the target tissue, transfer their therapeutic molecular cargo and improve their efficacy profile.
KEY SCIENTIFIC CONCEPTS OF REVIEW
Macrophage-mediated phagocytosis are the main responsible behind the short half-life in circulation of systemically injected exosomes, hindering their therapeutic effect. Exosomes 'Camouflage Cloak' strategy using antiphagocytic molecules can contribute to the inhibition of exosomal clearance, hence, increasing the on-target effect. Some candidate molecules that could exert an antiphagocytic role are CD47, CD24, CD44, CD31, β2M, PD-L1, App1, and DHMEQ. Pre- and post-isolation methods for exosome engineering are compatible with the loading of therapeutic cargo and the expression of antiphagocytic surface molecules.
Topics: B7-H1 Antigen; Biological Availability; Biological Mimicry; CD24 Antigen; CD47 Antigen; Drug Delivery Systems; Exosomes; Humans; Hyaluronan Receptors; Immune System; Macrophages; Mononuclear Phagocyte System; Phagocytes; Phagocytosis
PubMed: 34194832
DOI: 10.1016/j.jare.2021.01.001 -
Frontiers in Cellular and Infection... 2014Lipoarabinomannan is a major immunomodulatory lipoglycan found in the cell envelope of Mycobacterium tuberculosis and related human pathogens. It reproduces several... (Review)
Review
Lipoarabinomannan is a major immunomodulatory lipoglycan found in the cell envelope of Mycobacterium tuberculosis and related human pathogens. It reproduces several salient properties of M. tuberculosis in phagocytic cells, including inhibition of pro-inflammatory cytokine production, inhibition of phagolysosome biogenesis, and inhibition of apoptosis as well as autophagy. In this review, we present our current knowledge on lipoarabinomannan structure and ability to manipulate the endocytic pathway as well as phagocyte functions. A special focus is put on the molecular mechanisms employed and the signaling pathways hijacked. Available information is discussed in the context of M. tuberculosis pathogenesis.
Topics: Animals; Endocytosis; Humans; Lipopolysaccharides; Mycobacterium tuberculosis; Phagocytes; Phagocytosis; Tuberculosis
PubMed: 25629008
DOI: 10.3389/fcimb.2014.00187 -
Frontiers in Immunology 2020Tissue-resident phagocytes are responsible for the routine binding, engulfment, and resolution of their meals. Such populations of cells express appropriate surface... (Review)
Review
Tissue-resident phagocytes are responsible for the routine binding, engulfment, and resolution of their meals. Such populations of cells express appropriate surface receptors that are tailored to recognize the phagocytic targets of their niche and initiate the actin polymerization that drives internalization. Tissue-resident phagocytes also harbor enzymes and transporters along the endocytic pathway that orchestrate the resolution of ingested macromolecules from the phagolysosome. Solutes fluxed from the endocytic pathway and into the cytosol can then be reutilized by the phagocyte or exported for their use by neighboring cells. Such a fundamental metabolic coupling between resident phagocytes and the tissue in which they reside is well-emphasized in the case of retinal pigment epithelial (RPE) cells; specialized phagocytes that are responsible for the turnover of photoreceptor outer segments (POS). Photoreceptors are prone to photo-oxidative damage and their long-term health depends enormously on the disposal of aged portions of the outer segment. The phagocytosis of the POS by the RPE is the sole means of this turnover and clearance. RPE are themselves mitotically quiescent and therefore must resolve the ingested material to prevent their toxic accumulation in the lysosome that otherwise leads to retinal disorders. Here we describe the sequence of events underlying the healthy turnover of photoreceptors by the RPE with an emphasis on the signaling that ensures the phagocytosis of the distal POS and on the transport of solutes from the phagosome that supersedes its resolution. While other systems may utilize different receptors and transporters, the biophysical and metabolic manifestations of such events are expected to apply to all tissue-resident phagocytes that perform regular phagocytic programs.
Topics: Animals; Epithelial Cells; Humans; Phagocytes; Phagocytosis; Retinal Photoreceptor Cell Outer Segment; Retinal Pigment Epithelium; Signal Transduction
PubMed: 33281830
DOI: 10.3389/fimmu.2020.604205 -
Viruses Mar 2018Pattern recognition receptors (PRRs) sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is... (Review)
Review
Pattern recognition receptors (PRRs) sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is required to maintain intestinal barrier integrity and immune homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate immune defense against invasive pathogens in the intestine. Intestinal epithelial cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid tissues are critically involved in sensing components of the microbiome and regulating immune responses in the intestine to sustain immune tolerance against harmless antigens and to prevent inflammation. These processes have been mostly investigated in the context of the bacterial components of the microbiome so far. The impact of viruses residing in the intestine and the virus sensors, which are activated by these enteric viruses, on intestinal homeostasis and inflammation is just beginning to be unraveled. In this review, we will summarize recent findings indicating an important role of the enteric virome for intestinal homeostasis as well as pathology when the immune system fails to control the enteric virome. We will provide an overview of the virus sensors and signaling pathways, operative in the intestine and the mononuclear phagocyte subsets, which can sense viruses and shape the intestinal immune response. We will discuss how these might interact with resident enteric viruses directly or in context with the bacterial microbiome to affect intestinal homeostasis.
Topics: Animals; Biomarkers; Disease Susceptibility; Gastrointestinal Microbiome; Homeostasis; Host-Pathogen Interactions; Humans; Immunity, Innate; Immunity, Mucosal; Inflammation; Intestinal Mucosa; Intestines; Phagocytes; Receptors, Pattern Recognition; Signal Transduction
PubMed: 29570694
DOI: 10.3390/v10040146