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David A. Hume - One of the best experts on this subject based on the ideXlab platform.

  • the Mononuclear Phagocyte system of the rat
    Journal of Immunology, 2021
    Co-Authors: David A. Hume, Clare Pridans, Melanie Caruso, Sahar Keshvari, Omkar L Patkar, Anuj Sehgal, Stephen J Bush, Kim M Summers, Katharine M. Irvine
    Abstract:

    The laboratory rat continues to be the model of choice for many studies of physiology, behavior, and complex human diseases. Cells of the Mononuclear Phagocyte system (MPS; monocytes, macrophages, and dendritic cells) are abundant residents in every tissue in the body and regulate postnatal development, homeostasis, and innate and acquired immunity. Recruitment and proliferation of MPS cells is an essential component of both initiation and resolution of inflammation. The large majority of current knowledge of MPS biology is derived from studies of inbred mice, but advances in technology and resources have eliminated many of the advantages of the mouse as a model. In this article, we review the tools available and the current state of knowledge of development, homeostasis, regulation, and diversity within the MPS of the rat.

  • the equine Mononuclear Phagocyte system the relevance of the horse as a model for understanding human innate immunity
    Equine Veterinary Journal, 2020
    Co-Authors: Anna E Karagianni, David A. Hume, Zofia M Lisowski, Scott R Pirie
    Abstract:

    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.

  • The Mononuclear Phagocyte System: The Relationship between Monocytes and Macrophages.
    Trends in Immunology, 2018
    Co-Authors: David A. Hume, Katharine M. Irvine, Clare Pridans
    Abstract:

    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.

  • Homeostasis in the Mononuclear Phagocyte system
    Trends in Immunology, 2014
    Co-Authors: Stephen J. Jenkins, David A. Hume
    Abstract:

    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.

  • 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, 2011
    Co-Authors: Barry Bradford, David A. Hume, Neil A Mabbott
    Abstract:

    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, .

Muzlifah Haniffa - One of the best experts on this subject based on the ideXlab platform.

  • Mononuclear Phagocyte system
    eLS, 2017
    Co-Authors: Peter Vegh, James Fletcher, David Dixon, Muzlifah Haniffa
    Abstract:

    The Mononuclear Phagocyte system is part of the innate immune system and comprises dendritic cells (DCs), monocytes and macrophages, which fulfil a range of tasks essential for homeostasis and immunity. Macrophages and DCs were originally thought to be variations of monocytes, but recent evidence has defined the distinct origins of macrophages, monocytes and DCs. Mononuclear Phagocytes are functionally specialised and play a critical role in all phases of the immune response. They detect and phagocytose pathogens, recruit cells, initiate adaptive immunity by presenting antigens to T cells and coordinate the resolution of inflammation and wound healing. Macrophages have additional vital functions in tissue development and homeostasis. Key Concepts Mononuclear Phagocytes (dendritic cells, monocytes and macrophages) are a diverse group of cells with a wide range of functions essential for maintaining organism integrity. Macrophages are tissue resident, play a central role in homeostasis, perform tissue-specific functions and orchestrate immune responses. Dendritic cells are specialised antigen-presenting cells with superior ability to initiate immune responses. Monocytes are circulating leucocytes that can enter the tissue and have important roles in phagocytosis, inflammation and wound healing. Mononuclear Phagocytes coordinate innate and adaptive immune response. Keywords: macrophage; monocyte; dendritic cell; Mononuclear Phagocyte; phagocytosis; Kupffer cell; Langerhans cell; osteoclast; microglial cell

  • Comparative genomics analysis of Mononuclear Phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells
    Journal of Immunological Methods, 2016
    Co-Authors: Sabrina Carpentier, Muzlifah Haniffa, Florent Ginhoux, Thien-phong Vu Manh, Rabie Chelbi, Sandrine Henri, Bernard Malissen, Marc Dalod
    Abstract:

    Dendritic cells (DC) are Mononuclear Phagocytes which exhibit a branching (dendritic) morphology and excel at naive T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify Mononuclear Phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other Mononuclear Phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse Mononuclear Phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1(+) DCs, and between mouse and human Langerhans cells.

  • Human and Mouse Mononuclear Phagocyte Networks: A Tale of Two Species?
    Frontiers in immunology, 2015
    Co-Authors: Gary Reynolds, Muzlifah Haniffa
    Abstract:

    Dendritic cells (DCs), monocytes, and macrophages are a heterogeneous population of Mononuclear Phagocytes that are involved in antigen processing and presentation to initiate and regulate immune responses to pathogens, vaccines, tumor, and tolerance to self. In addition to their afferent sentinel function, DCs and macrophages are also critical as effectors and coordinators of inflammation and homeostasis in peripheral tissues. Harnessing DCs and macrophages for therapeutic purposes has major implications for infectious disease, vaccination, transplantation, tolerance induction, inflammation, and cancer immunotherapy. There has been a paradigm shift in our understanding of the developmental origin and function of the cellular constituents of the Mononuclear Phagocyte system. Significant progress has been made in tandem in both human and mouse Mononuclear Phagocyte biology. This progress has been accelerated by comparative biology analysis between mouse and human, which has proved to be an exceptionally fruitful strategy to harmonize findings across species. Such analyses have provided unexpected insights and facilitated productive reciprocal and iterative processes to inform our understanding of human and mouse Mononuclear Phagocytes. In this review, we discuss the strategies, power, and utility of comparative biology approaches to integrate recent advances in human and mouse Mononuclear Phagocyte biology and its potential to drive forward clinical translation of this knowledge. We also present a functional framework on the parallel organization of human and mouse Mononuclear Phagocyte networks.

  • human Mononuclear Phagocyte system reunited
    Seminars in Cell & Developmental Biology, 2015
    Co-Authors: Muzlifah Haniffa, Venetia Bigley, Matthew Collin
    Abstract:

    The human Mononuclear Phagocyte network comprises dendritic cells (DCs), monocytes and macrophages with a range of immune functions including antigen presentation linking innate and adaptive immunity. A number of DC, monocyte and macrophage subsets have been described in lymphoid and non-lymphoid tissues of mouse and human, with increased understanding of their distinct functional properties and genetic and cellular pathways of development. More recently, through comparative biology studies, a unified nomenclature of Mononuclear Phagocytes has begun to emerge with the identification of homologous subsets in several species. In this review, we discuss the current classification of human Mononuclear Phagocytes and the parallel organization of this network in the mouse. We also review the genetic control and developmental pathway of human Mononuclear Phagocytes and the immunological functions of the distinct subsets in health and inflammation.

Matthew Collin - One of the best experts on this subject based on the ideXlab platform.

  • The Mononuclear Phagocyte System in Organ Transplantation.
    American Journal of Transplantation, 2016
    Co-Authors: Jordi Ochando, Wing-hong Kwan, Florent Ginhoux, James A. Hutchinson, Daigo Hashimoto, Matthew Collin
    Abstract:

    The Mononuclear Phagocyte system (MPS) comprises monocytes, macrophages and dendritic cells (DCs). Over the past few decades, classification of the cells of the MPS has generated considerable controversy. Recent studies into the origin, developmental requirements and function of MPS cells are beginning to solve this problem in an objective manner. Using high-resolution genetic analyses and fate-mapping studies, three main Mononuclear Phagocyte lineages have been defined, namely, macrophage populations established during embryogenesis, monocyte-derived cells that develop during adult life and DCs. These subsets and their diverse subsets have specialized functions that are largely conserved between species, justifying the introduction of a new, universal scheme of nomenclature and providing the framework for therapeutic manipulation of immune responses in the clinic. In this review, we have commented on the implications of this novel MPS classification in solid organ transplantation.

  • human Mononuclear Phagocyte system reunited
    Seminars in Cell & Developmental Biology, 2015
    Co-Authors: Muzlifah Haniffa, Venetia Bigley, Matthew Collin
    Abstract:

    The human Mononuclear Phagocyte network comprises dendritic cells (DCs), monocytes and macrophages with a range of immune functions including antigen presentation linking innate and adaptive immunity. A number of DC, monocyte and macrophage subsets have been described in lymphoid and non-lymphoid tissues of mouse and human, with increased understanding of their distinct functional properties and genetic and cellular pathways of development. More recently, through comparative biology studies, a unified nomenclature of Mononuclear Phagocytes has begun to emerge with the identification of homologous subsets in several species. In this review, we discuss the current classification of human Mononuclear Phagocytes and the parallel organization of this network in the mouse. We also review the genetic control and developmental pathway of human Mononuclear Phagocytes and the immunological functions of the distinct subsets in health and inflammation.

Siamon Gordon - One of the best experts on this subject based on the ideXlab platform.

  • csf1r defines the Mononuclear Phagocyte system lineage in human blood in health and covid 19
    Immunotherapy Advances, 2021
    Co-Authors: Theo W Combes, Siamon Gordon, Federica Orsenigo, Alexander J Stewart, A Jeewaka S R Mendis, Deborah K Dunnwalters, Fernando O Martinez
    Abstract:

    Mononuclear Phagocytes defend tissues, present antigens and mediate recovery and healing To date we lack a marker to unify Mononuclear Phagocytes in humans or that informs us about their origin Here, we reassess Mononuclear Phagocyte ontogeny in human blood through the lineage receptor CSF1R, in the steady state and in COVID-19 We define CSF1R as the first sensitive and reproducible pan-Phagocyte lineage marker, to identify and enumerate all conventional monocytes, and the myeloid dendritic cells In the steady state CSF1R is sufficient for sorting and immuno-magnetic isolation In pathology, changes in CSF1R are more sensitive than CD14 and CD16 In COVID-19, a significant drop in membrane CSF1R is useful for stratifying patients, beyond the power of cell categories published thus far, which fail to capture COVID-19 specific events Importantly, CSF1R defines cells which are neither conventional monocytes nor DCs, which are missed in published analysis CSF1R decrease can be linked ex vivo to high CSF1 levels Blood assessment of CSF1R+ cells opens a developmental window to the Mononuclear Phagocyte System in transit from bone marrow to tissues, supports isolation and phenotypic characterisation, identifies novel cell types, and singles out CSF1R inhibition as therapeutic target in COVID-19 and other diseases

  • From the Reticuloendothelial to Mononuclear Phagocyte System - The Unaccounted Years.
    Frontiers in Immunology, 2015
    Co-Authors: Simon Yona, Siamon Gordon
    Abstract:

    It is over 125 years since Ilya Metchnikoff described the significance of phagocytosis. In this review we examine the early origins and development of macrophage research continuing after his death in 1916, through the period of the Reticulo-Endothelial System. Studies on these cells resulted in a substantial literature spanning immunology, haematology, biochemistry and pathology. Early histological studies on morphology and in situ labelling laid the foundations to appreciate the diversity and functional capacity of these cells in the steady state and during pathology. We complete this Phagocyte retrospective with the establishment of the Mononuclear Phagocyte System nomenclature half a century ago.

  • THE Mononuclear Phagocyte SYSTEM OF THE MOUSE DEFINED BY IMMUNOHISTOCHEMICAL LOCALIZATION OF ANTIGEN F4/80 Relationship Between Macrophages, Langerhans Cells, Reticular Cells,
    2013
    Co-Authors: Dendritic Cells In Lymphoid, Anne P Robinson, Gordon G Macpherson, Hematopoietic Organs, A. Hume, Siamon Gordon
    Abstract:

    The immune response genes of the major histocompatibility gene complex code for surface antigens (Ia) now believed to be involved in the interaction between T cells and accessory or "antigen-presenting " cells (1, 2). Whilst some groups suggest that Ia antigens present on subpopulations of Mononuclear Phagocytes are involved in T cell activation (1-4), others have presented evidence for the involvement of a separate Ia + cell population (5-8) now generally referred to as dendritic cells. The in vivo correlate of the isolated antigen-presenting dendritic cell is not yet clear. The availability of a specific monoclonal antibody against mouse dendritic cells (9) will be helpful in clarifying this question. One obvious candidate is the Ia + "interdigitating cell " that has been described in thymus and in T cell-dependent areas of lymphoid organs (10-15). However, whilst the isolated splenic dendritic cell has virtually none of the functional characteristics of a Mononuclear Phagocyte (6), it has been suggested that interdigitating cells are members of the Mononuclear Phagocyte system and are related to epidermal Langerhans cells and similar cells.found in afferent lymphatic

  • unravelling Mononuclear Phagocyte heterogeneity
    Nature Reviews Immunology, 2010
    Co-Authors: Frederic Geissmann, David A. Hume, Siamon Gordon, Allan Mci Mowat, Gwendalyn J Randolph
    Abstract:

    When Ralph Steinman and Zanvil Cohn first described dendritic cells (DCs) in 1973 it took many years to convince the immunology community that these cells were truly distinct from macrophages. Almost four decades later, the DC is regarded as the key initiator of adaptive immune responses; however, distinguishing DCs from macrophages still leads to confusion and debate in the field. Here, Nature Reviews Immunology asks five experts to discuss the issue of heterogeneity in the Mononuclear Phagocyte system and to give their opinion on the importance of defining these cells for future research.

Robert Sackstein - One of the best experts on this subject based on the ideXlab platform.

  • e selectin ligands in the human Mononuclear Phagocyte system implications for infection inflammation and immunotherapy
    Frontiers in Immunology, 2018
    Co-Authors: Mariana Silva, Paula A Videira, Robert Sackstein
    Abstract:

    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.

  • E-Selectin Ligands in the Human Mononuclear Phagocyte System: Implications for Infection, Inflammation, and Immunotherapy
    Frontiers Media S.A., 2018
    Co-Authors: Mariana Silva, Paula A Videira, Robert Sackstein
    Abstract:

    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