The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform
David A. Hume - One of the best experts on this subject based on the ideXlab platform.
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the equine Mononuclear Phagocyte System the relevance of the horse as a model for understanding human innate immunity
Equine Veterinary Journal, 2020Co-Authors: Anna E Karagianni, David A. Hume, Zofia M Lisowski, Scott R PirieAbstract:The Mononuclear Phagocyte System (MPS) is a family of cells of related function that includes bone marrow progenitors, blood monocytes and resident tissue macrophages. Macrophages are effector cells in both innate and acquired immunity. They are a major resident cell population in every organ and their numbers increase in response to proinflammatory stimuli. Their function is highly regulated by a wide range of agonists, including lymphokines, cytokines and products of microorganisms. Macrophage biology has been studied most extensively in mice, yet direct comparisons of rodent and human macrophages have revealed many functional differences. In this review, we provide an overview of the equine MPS, describing the variation in the function and phenotype of macrophages depending on their location and the similarities and differences between the rodent, human and equine immune response. We discuss the use of the horse as a large animal model in which to study macrophage biology and pathological processes shared with humans. Finally, following the recent update to the horse genome, facilitating further comparative analysis of regulated gene expression between the species, we highlight the importance of future transcriptomic macrophage studies in the horse, the findings of which may also be applicable to human as well as veterinary research.
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The Mononuclear Phagocyte System: The Relationship between Monocytes and Macrophages.
Trends in Immunology, 2018Co-Authors: David A. Hume, Katharine M. Irvine, Clare PridansAbstract:The Mononuclear Phagocyte System (MPS) is defined as a cell lineage in which committed marrow progenitors give rise to blood monocytes and tissue macrophages. Here, we discuss the concept of self-proscribed macrophage territories and homeostatic regulation of tissue macrophage abundance through growth factor availability. Recent studies have questioned the validity of the MPS model and argued that tissue-resident macrophages are a separate lineage seeded during development and maintained by self-renewal. We address this issue; discuss the limitations of inbred mouse models of monocyte-macrophage homeostasis; and summarize the evidence suggesting that during postnatal life, monocytes can replace resident macrophages in all major organs and adopt their tissue-specific gene expression. We conclude that the MPS remains a valid and accurate framework for understanding macrophage development and homeostasis.
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Homeostasis in the Mononuclear Phagocyte System
Trends in Immunology, 2014Co-Authors: Stephen J. Jenkins, David A. HumeAbstract:The Mononuclear Phagocyte System (MPS) is a family of functionally related cells including bone marrow precursors, blood monocytes, and tissue macrophages. We review the evidence that macrophages and dendritic cells (DCs) are separate lineages and functional entities, and examine whether the traditional view that monocytes are the immediate precursors of tissue macrophages needs to be refined based upon evidence that macrophages can extensively self-renew and can be seeded from yolk sac/foetal liver progenitors with little input from monocytes thereafter. We review the role of the growth factor colony-stimulating factor (CSF)1, and present a model consistent with the concept of the MPS in which local proliferation and monocyte recruitment are connected to ensure macrophages occupy their well-defined niche in most tissues.
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defining anatomical localisation and subsets of the murine Mononuclear Phagocyte System using integrin alpha x itgax cd11c and colony stimulating factor 1 receptor csf1 r cd115 expression fails to discriminate macrophages from dendritic cells
15th International Conference of Mucosal Immunology, 2011Co-Authors: Barry Bradford, David A. Hume, Neil A MabbottAbstract:Citation for published version: Bradford, B, Hume, D & Mabbott, N 2011, 'Defining anatomical localisation and subsets of the murine Mononuclear Phagocyte System using integrin alpha X (ITGAX/CD11c) and colony stimulating factor 1 receptor (CSF1-R/CD115) expression fails to discriminate macrophages from dendritic cells' 15th International Conference of Mucosal Immunology, Paris, France, 6/07/11 9/07/11, .
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The Mononuclear Phagocyte System of the pig as a model for understanding human innate immunity and disease
Journal of Leukocyte Biology, 2011Co-Authors: Lynsey Fairbairn, Ronan Kapetanovic, David P Sester, David A. HumeAbstract:The biology of cells of the Mononuclear Phagocyte System has been studied extensively in the mouse. Studies of the pig as an experimental model have commonly been consigned to specialist animal science journals. In this review, we consider some of the many ways in which the innate immune Systems of humans differ from those of mice, the ways that pigs may address the shortcomings of mice as models for the study of macrophage differentiation and activation in vitro, and the biology of sepsis and other pathologies in the living animal. With the completion of the genome sequence and the characterization of many key regulators and markers, the pig has emerged as a tractable model of human innate immunity and disease that should address the limited, predictive value of rodents in preclinical studies.
Robert Sackstein - One of the best experts on this subject based on the ideXlab platform.
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e selectin ligands in the human Mononuclear Phagocyte System implications for infection inflammation and immunotherapy
Frontiers in Immunology, 2018Co-Authors: Mariana Silva, Paula A Videira, Robert SacksteinAbstract:The Mononuclear Phagocyte System (MPS) comprises a network of circulating monocytes and dendritic cells (DCs), and “histiocytes” (tissue-resident macrophages and DCs) that are derived in part from blood-borne monocytes and DCs. The capacity of circulating monocytes and DCs to function as the body’s first-line defense against offending pathogens greatly depends on their ability to egress the bloodstream and infiltrate inflammatory sites. Extravasation involves a sequence of coordinated molecular events and is initiated by E-selectin-mediated deceleration of the circulating leukocytes onto microvascular endothelial cells of the target tissue. E-selectin is inducibly expressed by cytokines (TNF-α and IL-1β) on inflamed endothelium, and binds to sialofucosylated glycan determinants displayed on protein and lipid scaffolds of blood cells. Efficient extravasation of circulating monocytes and DCs to inflamed tissues is crucial in facilitating an effective immune response, but also fuels the immunopathology of several inflammatory disorders. Thus, insights into the structural and functional properties of the E-selectin ligands expressed by different monocyte and DC populations is key to understanding the biology of protective immunity and the pathobiology of several acute and chronic inflammatory diseases. This review will address the role of E-selectin in recruitment of human circulating monocytes and DCs to sites of tissue injury/inflammation, the structural biology of the E-selectin ligands expressed by these cells, and the molecular effectors that shape E-selectin ligand cell-specific display. Additionally, therapeutic approaches targeting E-selectin receptor/ligand interactions, which can be used to boost host defense or, conversely, to dampen pathological inflammatory conditions, will also be discussed.
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E-Selectin Ligands in the Human Mononuclear Phagocyte System: Implications for Infection, Inflammation, and Immunotherapy
Frontiers Media S.A., 2018Co-Authors: Mariana Silva, Paula A Videira, Robert SacksteinAbstract:The Mononuclear Phagocyte System comprises a network of circulating monocytes and dendritic cells (DCs), and “histiocytes” (tissue-resident macrophages and DCs) that are derived in part from blood-borne monocytes and DCs. The capacity of circulating monocytes and DCs to function as the body’s first-line defense against offending pathogens greatly depends on their ability to egress the bloodstream and infiltrate inflammatory sites. Extravasation involves a sequence of coordinated molecular events and is initiated by E-selectin-mediated deceleration of the circulating leukocytes onto microvascular endothelial cells of the target tissue. E-selectin is inducibly expressed by cytokines (tumor necrosis factor-α and IL-1β) on inflamed endothelium, and binds to sialofucosylated glycan determinants displayed on protein and lipid scaffolds of blood cells. Efficient extravasation of circulating monocytes and DCs to inflamed tissues is crucial in facilitating an effective immune response, but also fuels the immunopathology of several inflammatory disorders. Thus, insights into the structural and functional properties of the E-selectin ligands expressed by different monocyte and DC populations is key to understanding the biology of protective immunity and the pathobiology of several acute and chronic inflammatory diseases. This review will address the role of E-selectin in recruitment of human circulating monocytes and DCs to sites of tissue injury/inflammation, the structural biology of the E-selectin ligands expressed by these cells, and the molecular effectors that shape E-selectin ligand cell-specific display. In addition, therapeutic approaches targeting E-selectin receptor/ligand interactions, which can be used to boost host defense or, conversely, to dampen pathological inflammatory conditions, will also be discussed
Gina Song - One of the best experts on this subject based on the ideXlab platform.
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Mononuclear Phagocyte System function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients
Cancer Chemotherapy and Pharmacology, 2019Co-Authors: Brittney Roberts Starling, Gina Song, Parag Kumar, Andrew T Lucas, David A Barrow, Laura Farnan, Laura H Hendrix, Hugh GiovinazzoAbstract:Obesity may alter Mononuclear Phagocyte System (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer. Hormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured. A separate pharmacology study was performed that evaluated the relationship between serum hormone concentrations, MPS function, and PK disposition of PLD in refractory ovarian cancer patients. Univariate analysis revealed a significant relationship between serum estradiol and body mass index (OR 8.64, 95% CI 2.67–28.0, p < 0.001). Estrone and testosterone concentrations were positively correlated with MPS function (ρ = 0.57 and 0.53, p = 0.14 and 0.18, respectively) and inversely correlated with PLD PK exposure (ρ = − 0.75 and − 0.76, respectively, p = 0.02 for both). Higher MPS function resulting in reduced PLD exposure is a potential mechanism for reduced efficacy of PLD and other nanoparticles observed in obese patients with cancer. PK simulations suggest higher doses of PLD are required in obese patients to achieve similar exposures as standard dosing in normal weight patients.
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Nanoparticles and the Mononuclear Phagocyte System: pharmacokinetics and applications for inflammatory diseases.
Current Rheumatology Reviews, 2014Co-Authors: Gina Song, Jennifer S. Petschauer, Andrew J. Madden, William C. ZamboniAbstract:Nanoparticles (NPs) provide several advantages over the small molecule drugs including prolonged circulation time and enhanced delivery to targeted sites. Once a NP enters the body, it interacts with host’s immune System and is engulfed by cells of the Mononuclear Phagocyte System (MPS). The interaction between NPs and the immune cells can result in immunosuppression or immunostimulation, which may enhance or reduce the treatment effects of NPs. Therefore, it is critical to understand the interactions between NPs and the immune System in order to optimize the treatment benefit and minimize the undesirable toxicities of NPs. This review elaborates on the interaction between NP and the MPS and its impacts on the pharmacokinetics (PK) and pharmacodynamics (PD) of NPs and applications for inflammatory diseases. This review also encompasses an overview of NPs being developed for treatment of inflammatory diseases.
Hugues Lelouard - One of the best experts on this subject based on the ideXlab platform.
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the peyer s patch Mononuclear Phagocyte System at steady state and during infection
Frontiers in Immunology, 2017Co-Authors: Clément Da Silva, Johnny Bonnardel, Jean-pierre Gorvel, Camille Wagner, Hugues LelouardAbstract:The gut represents a potential entry site for a wide range of pathogens including protozoa, bacteria, viruses or fungi. Consequently, it is protected by one of the largest and most diversified population of immune cells of the body. Its surveillance requires the constant sampling of its encounters by dedicated sentinels composed of follicles and their associated epithelium located in specialized area. In the small intestine, Peyer’s patches (PP) are the most important of these mucosal immune response inductive sites. Through several mechanisms including transcytosis by specialized epithelial cells called M-cells, access to the gut lumen is facilitated in PPs. Although antigen sampling is critical to the initiation of the mucosal immune response, pathogens have evolved strategies to take advantage of this permissive gateway to enter the host and disseminate. It is therefore critical to decipher the mechanisms that underlie both host defense and pathogen subversive strategies in order to develop new mucosal-based therapeutic approaches. Whereas penetration of pathogens through M cells has been well described, their fate once they have reached the subepithelial dome remains less well understood. Nevertheless, it is clear that the Mononuclear Phagocyte System (MPS) plays a critical role in handling these pathogens. MPS members, including both dendritic cells and macrophages, are indeed strongly enriched in the subepithelial dome, interact with M cells and are necessary for antigen presentation to immune effector cells. This review focuses on recent advances, which have allowed distinguishing the different PP Mononuclear Phagocyte subsets. It gives an overview of their diversity, specificity, location and functions. Interaction of PP Phagocytes with the microbiota and the follicle-associated epithelium as well as PP infection studies are described in the light of these new criteria of PP Phagocyte identification. Finally, known alterations affecting the different Phagocyte subsets during PP stimulation or infection are discussed.
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The Peyer’s Patch Mononuclear Phagocyte System at Steady State and during Infection
Frontiers Media S.A., 2017Co-Authors: Clément Da Silva, Johnny Bonnardel, Jean-pierre Gorvel, Camille Wagner, Hugues LelouardAbstract:The gut represents a potential entry site for a wide range of pathogens including protozoa, bacteria, viruses, or fungi. Consequently, it is protected by one of the largest and most diversified population of immune cells of the body. Its surveillance requires the constant sampling of its encounters by dedicated sentinels composed of follicles and their associated epithelium located in specialized area. In the small intestine, Peyer’s patches (PPs) are the most important of these mucosal immune response inductive sites. Through several mechanisms including transcytosis by specialized epithelial cells called M-cells, access to the gut lumen is facilitated in PPs. Although antigen sampling is critical to the initiation of the mucosal immune response, pathogens have evolved strategies to take advantage of this permissive gateway to enter the host and disseminate. It is, therefore, critical to decipher the mechanisms that underlie both host defense and pathogen subversive strategies in order to develop new mucosal-based therapeutic approaches. Whereas penetration of pathogens through M cells has been well described, their fate once they have reached the subepithelial dome (SED) remains less well understood. Nevertheless, it is clear that the Mononuclear Phagocyte System (MPS) plays a critical role in handling these pathogens. MPS members, including both dendritic cells and macrophages, are indeed strongly enriched in the SED, interact with M cells, and are necessary for antigen presentation to immune effector cells. This review focuses on recent advances, which have allowed distinguishing the different PP Mononuclear Phagocyte subsets. It gives an overview of their diversity, specificity, location, and functions. Interaction of PP Phagocytes with the microbiota and the follicle-associated epithelium as well as PP infection studies are described in the light of these new criteria of PP Phagocyte identification. Finally, known alterations affecting the different Phagocyte subsets during PP stimulation or infection are discussed
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Gene expression profiling of the Peyer's patch Mononuclear Phagocyte System
Genomics data, 2015Co-Authors: Johnny Bonnardel, Clément Da Silva, Marion Massé, Frederic Montañana-sanchis, Jean-pierre Gorvel, Hugues LelouardAbstract:Peyer's patches (PPs) are primary inductive sites of mucosal immunity. The PP Mononuclear Phagocyte System, which encompasses both dendritic cells (DCs) and macrophages, is essential for the initiation of the mucosal immune response. We recently developed a method to isolate each Mononuclear Phagocyte subset of PP (Bonnardel et al., 2015). We performed a transcriptional analysis of three of these subsets: the CD11b(+) conventional DC, the lysozyme-expressing monocyte-derived DC termed LysoDC and the CD11c(hi) lysozyme-expressing macrophages. Here, we provide details of the gating strategy we used to isolate each Phagocyte subset and show the quality controls and analysis associated with our gene array data deposited into Gene Expression Omnibus (GEO) under GSE65514.
Scott R Pirie - One of the best experts on this subject based on the ideXlab platform.
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the equine Mononuclear Phagocyte System the relevance of the horse as a model for understanding human innate immunity
Equine Veterinary Journal, 2020Co-Authors: Anna E Karagianni, David A. Hume, Zofia M Lisowski, Scott R PirieAbstract:The Mononuclear Phagocyte System (MPS) is a family of cells of related function that includes bone marrow progenitors, blood monocytes and resident tissue macrophages. Macrophages are effector cells in both innate and acquired immunity. They are a major resident cell population in every organ and their numbers increase in response to proinflammatory stimuli. Their function is highly regulated by a wide range of agonists, including lymphokines, cytokines and products of microorganisms. Macrophage biology has been studied most extensively in mice, yet direct comparisons of rodent and human macrophages have revealed many functional differences. In this review, we provide an overview of the equine MPS, describing the variation in the function and phenotype of macrophages depending on their location and the similarities and differences between the rodent, human and equine immune response. We discuss the use of the horse as a large animal model in which to study macrophage biology and pathological processes shared with humans. Finally, following the recent update to the horse genome, facilitating further comparative analysis of regulated gene expression between the species, we highlight the importance of future transcriptomic macrophage studies in the horse, the findings of which may also be applicable to human as well as veterinary research.