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Trends in Microbiology Mar 2022Glycans are expressed on the surface of nearly all host and bacterial cells. Not surprisingly, glycan-mediated molecular interactions play a vital role in bacterial... (Review)
Review
Glycans are expressed on the surface of nearly all host and bacterial cells. Not surprisingly, glycan-mediated molecular interactions play a vital role in bacterial pathogenesis and host responses against pathogens. Glycan-mediated host-pathogen interactions can benefit the pathogen, host, or both. Here, we discuss (i) bacterial glycans that play a critical role in bacterial colonization and/or immune evasion, (ii) host glycans that are utilized by bacteria for pathogenesis, and (iii) bacterial and host glycans involved in immune responses against pathogens. We further discuss (iv) opportunities and challenges for transforming these research findings into more effective antibacterial strategies, and (v) technological advances in glycoscience that have helped to accelerate progress in research. These studies collectively offer valuable insights into new perspectives on antibacterial strategies that may effectively tackle the drug-resistant pathogens that are rapidly spreading globally.
Topics: Bacteria; Host-Pathogen Interactions; Immune Evasion; Phagocytosis; Polysaccharides; Polysaccharides, Bacterial
PubMed: 34274195
DOI: 10.1016/j.tim.2021.06.011 -
ELife Nov 2022A network of open channels allows cells and molecular cargo to travel from the center to the periphery of lab-grown colonies of , helping to eradicate competing species.
A network of open channels allows cells and molecular cargo to travel from the center to the periphery of lab-grown colonies of , helping to eradicate competing species.
Topics: Staphylococcus aureus; Biofilms; Pseudomonas aeruginosa; Phagocytosis
PubMed: 36322127
DOI: 10.7554/eLife.83789 -
Nephron 2022Various forms of cell death have been identified, and billions of cells die during development and daily in adult organisms. Clearing dead cells and associated cellular... (Review)
Review
Various forms of cell death have been identified, and billions of cells die during development and daily in adult organisms. Clearing dead cells and associated cellular debris is an integral part of tissue homeostasis. While diverse types of phagocytes remove various forms of dying cells during acute kidney injury (AKI), it remains unknown whether boosting removal of a specific form of dying cell would provide a benefit and which cell type should be targeted for phagocytosis-mediated therapy. As there is a lack of viable strategies for the prevention and treatment of AKI, novel therapies and innovative approaches are required. There is a strong demand on developing and analyzing novel models to boost, monitor, and stop phagocytosis of dying cells.
Topics: Acute Kidney Injury; Apoptosis; Cell Death; Female; Humans; Male; Phagocytes; Phagocytosis
PubMed: 34284391
DOI: 10.1159/000517731 -
Nature Communications Sep 2023GPR84 is a unique orphan G protein-coupled receptor (GPCR) that can be activated by endogenous medium-chain fatty acids (MCFAs). The signaling of GPR84 is largely...
GPR84 is a unique orphan G protein-coupled receptor (GPCR) that can be activated by endogenous medium-chain fatty acids (MCFAs). The signaling of GPR84 is largely pro-inflammatory, which can augment inflammatory response, and GPR84 also functions as a pro-phagocytic receptor to enhance phagocytic activities of macrophages. In this study, we show that the activation of GPR84 by the synthetic agonist 6-OAU can synergize with the blockade of CD47 on cancer cells to induce phagocytosis of cancer cells by macrophages. We also determine a high-resolution structure of the GPR84-G signaling complex with 6-OAU. This structure reveals an occluded binding pocket for 6-OAU, the molecular basis of receptor activation involving non-conserved structural motifs of GPR84, and an unusual G-coupling interface. Together with computational docking and simulations studies, this structure also suggests a mechanism for the high selectivity of GPR84 for MCFAs and a potential routes of ligand binding and dissociation. These results provide a framework for understanding GPR84 signaling and developing new drugs targeting GPR84.
Topics: Phagocytes; Signal Transduction; Macrophages; Phagocytosis; Fatty Acids
PubMed: 37709767
DOI: 10.1038/s41467-023-41201-0 -
Glia Jun 2022Elimination of dead or live cells take place in both a healthy and diseased central nervous system (CNS). Dying or dead cells are quickly cleared by phagocytosis for the... (Review)
Review
Elimination of dead or live cells take place in both a healthy and diseased central nervous system (CNS). Dying or dead cells are quickly cleared by phagocytosis for the maintenance of a healthy CNS or for recovery after injury. Live cells or parts thereof, such as the synapses and myelin, are appropriately eliminated by phagocytosis to maintain or refine neural networks during development and adulthood. Microglia, the specific population of resident macrophages in the CNS, are classically considered as primary phagocytes; however, astrocytes have also been highlighted as phagocytes in the last decade. Phagocytic targets and receptors are reported to be mostly common between astrocytes and microglia, which raises the question of how astrocytic phagocytosis differs from microglial phagocytosis, and how these two phagocytic systems cooperate. In this review, we address the consequences of astrocytic phagocytosis, particularly focusing on these elusive points.
Topics: Astrocytes; Central Nervous System; Microglia; Phagocytes; Phagocytosis
PubMed: 35142399
DOI: 10.1002/glia.24145 -
Blood Jun 2022
Topics: B7-H1 Antigen; Extracellular Vesicles; Humans; Macrophages; Neoplasms; Phagocytosis; Tumor Suppressor Protein p53
PubMed: 35737407
DOI: 10.1182/blood.2022016100 -
Cell Host & Microbe Aug 2021Immune deactivation of phagocytes is a central event in the pathogenesis of sepsis. Herein, we identify a master regulatory role of IL-6 signaling on LC3-associated...
Immune deactivation of phagocytes is a central event in the pathogenesis of sepsis. Herein, we identify a master regulatory role of IL-6 signaling on LC3-associated phagocytosis (LAP) and reveal that uncoupling of these two processes during sepsis induces immunoparalysis in monocytes/macrophages. In particular, we demonstrate that activation of LAP by the human fungal pathogen Aspergillus fumigatus depends on ERK1/2-mediated phosphorylation of p47phox subunit of NADPH oxidase. Physiologically, autocrine IL-6/JAK2/Ninein axis orchestrates microtubule organization and dynamics regulating ERK recruitment to the phagosome and LC3 phagosome (LAPosome) formation. In sepsis, loss of IL-6 signaling specifically abrogates microtubule-mediated trafficking of ERK, leading to defective activation of LAP and impaired killing of bacterial and fungal pathogens by monocytes/macrophages, which can be selectively restored by IL-6 supplementation. Our work uncovers a molecular pathway linking IL-6 signaling with LAP and provides insight into the mechanisms underlying immunoparalysis in sepsis.
Topics: Aspergillus fumigatus; Cytokines; Cytoskeletal Proteins; Humans; Interleukin-6; Janus Kinase 2; Macrophages; Microtubule-Associated Proteins; Monocytes; Nuclear Proteins; Phagocytes; Phagocytosis; Sepsis; Signal Transduction
PubMed: 34214493
DOI: 10.1016/j.chom.2021.06.002 -
International Journal of Molecular... Aug 2019The immune response is essential to protect organisms from infection and an altered self. An organism's overall metabolic status is now recognized as an important and... (Review)
Review
The immune response is essential to protect organisms from infection and an altered self. An organism's overall metabolic status is now recognized as an important and long-overlooked mediator of immunity and has spurred new explorations of immune-related metabolic abnormalities. Peroxisomes are essential metabolic organelles with a central role in the synthesis and turnover of complex lipids and reactive species. Peroxisomes have recently been identified as pivotal regulators of immune functions and inflammation in the development and during infection, defining a new branch of immunometabolism. This review summarizes the current evidence that has helped to identify peroxisomes as central regulators of immunity and highlights the peroxisomal proteins and metabolites that have acquired relevance in human pathologies for their link to the development of inflammation, neuropathies, aging and cancer. This review then describes how peroxisomes govern immune signaling strategies such as phagocytosis and cytokine production and their relevance in fighting bacterial and viral infections. The mechanisms by which peroxisomes either control the activation of the immune response or trigger cellular metabolic changes that activate and resolve immune responses are also described.
Topics: Aging; Animals; Biomarkers; Disease Susceptibility; Energy Metabolism; Host-Pathogen Interactions; Humans; Immunity; Immunomodulation; Inflammation; Peroxisomes; Phagocytosis; Signal Transduction
PubMed: 31398943
DOI: 10.3390/ijms20163877 -
Chemico-biological Interactions Jan 2022Boosting or suppressing our immune system represents an attractive adjunct in the treatment of infections including SARS-CoV-2, cancer, AIDS, malnutrition, age related... (Review)
Review
Boosting or suppressing our immune system represents an attractive adjunct in the treatment of infections including SARS-CoV-2, cancer, AIDS, malnutrition, age related problems and some inflammatory disorders. Thus, there has been a growing interest in exploring and developing novel drugs, natural or synthetic, that can manipulate our defence mechanism. Many of such studies, reported till date, have been designed to explore effect of the therapeutic on function of macrophages, being a key component in innate immune system. Indeed, RAW264.7, J774A.1, THP-1 and U937 cell lines act as ideal model systems for preliminary investigation and selection of dose for in vivo studies. Several bioassays have been standardized so far where many techniques require high throughput instruments, cost effective reagents and technical assistance that may hinder many scholars to perform a method demanding compilation of available protocols. In this review, we have taken an attempt for the first time to congregate commonly used in vitro immune-modulating techniques explaining their principles. The study detected that among about 40 different assays and more than 150 sets of primers, the methods of cell proliferation by MTT, phagocytosis by neutral red, NO detection by Griess reaction and estimation of expression of TLRs, COX-2, iNOS, TNF-α, IL-6 and IL-1β by PCR have been the most widely used to screen the therapeutics under investigation.
Topics: Animals; Cell Line; Cell Line, Tumor; Cell Proliferation; Humans; Immunity, Innate; Immunomodulation; Inflammation; Phagocytosis
PubMed: 34906553
DOI: 10.1016/j.cbi.2021.109776 -
Current Opinion in Pulmonary Medicine Jan 2020Asthma is a chronic inflammatory disease in which changes in macrophage polarization have been shown to contribute to the pathogenesis. The present review discusses the... (Review)
Review
PURPOSE OF REVIEW
Asthma is a chronic inflammatory disease in which changes in macrophage polarization have been shown to contribute to the pathogenesis. The present review discusses the contribution of changes in macrophage function to asthma related to polarization changes and elaborates on possible therapeutic strategies targeting macrophage function and polarization.
RECENT FINDINGS
Macrophage function alterations were shown to contribute to asthma pathology in several ways. One is by impaired phagocytosis and efferocytosis. Another is by changing inflammation, by altered (anti)inflammatory cytokine production and induction of the inflammasome. Finally, macrophages can contribute to remodeling in asthma, although little evidence is present in humans yet.Novel therapeutic strategies targeting macrophages include dampening inflammation by changing polarization or by inhibiting the NLRP3 inflammasome, and by targeting efferocytosis. However, many of these studies were performed in animal models leaving their translation to the clinic for future research.
SUMMARY
The present review emphasizes the contribution of altered macrophage function to asthma, gives insight in possible new therapeutic strategies targeting macrophages, and indicates which knowledge gaps remain open.
Topics: Animals; Asthma; Cell Polarity; Humans; Inflammation; Macrophages, Alveolar; Phagocytosis
PubMed: 31703000
DOI: 10.1097/MCP.0000000000000647