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Monocyte, Macrophage, and Dendritic Cell Development: the Human Perspective

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  • Authors: Matthew Collin1, Venetia Bigley2
  • Editor: Siamon Gordon3
    Affiliations: 1: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom; 2: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom; 3: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0015-2015
  • Received 16 July 2015 Accepted 19 April 2016 Published 16 September 2016
  • Matthew Collin, [email protected]
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  • Abstract:

    The maintenance of monocytes, macrophages, and dendritic cells (DCs) involves manifold pathways of ontogeny and homeostasis that have been the subject of intense study in recent years. The concept of a peripheral mononuclear phagocyte system continually renewed by blood-borne monocytes has been modified to include specialized DC pathways of development that do not involve monocytes, and longevity through self-renewal of tissue macrophages. The study of development remains difficult owing to the plasticity of phenotypes and misconceptions about the fundamental structure of hematopoiesis. However, greater clarity has been achieved in distinguishing inflammatory monocyte-derived DCs from DCs arising in the steady state, and new concepts of conjoined lymphomyeloid hematopoiesis more easily accommodate the shared lymphoid and myeloid phenotypes of some DCs. Cross-species comparisons have also yielded coherent systems of nomenclature for all mammalian monocytes, macrophages, and DCs. Finally, the clear relationships between ontogeny and functional specialization offer information about the regulation of immune responses and provide new tools for the therapeutic manipulation of myeloid mononuclear cells in medicine.

  • Citation: Collin M, Bigley V. 2016. Monocyte, Macrophage, and Dendritic Cell Development: the Human Perspective. Microbiol Spectrum 4(5):MCHD-0015-2015. doi:10.1128/microbiolspec.MCHD-0015-2015.


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The maintenance of monocytes, macrophages, and dendritic cells (DCs) involves manifold pathways of ontogeny and homeostasis that have been the subject of intense study in recent years. The concept of a peripheral mononuclear phagocyte system continually renewed by blood-borne monocytes has been modified to include specialized DC pathways of development that do not involve monocytes, and longevity through self-renewal of tissue macrophages. The study of development remains difficult owing to the plasticity of phenotypes and misconceptions about the fundamental structure of hematopoiesis. However, greater clarity has been achieved in distinguishing inflammatory monocyte-derived DCs from DCs arising in the steady state, and new concepts of conjoined lymphomyeloid hematopoiesis more easily accommodate the shared lymphoid and myeloid phenotypes of some DCs. Cross-species comparisons have also yielded coherent systems of nomenclature for all mammalian monocytes, macrophages, and DCs. Finally, the clear relationships between ontogeny and functional specialization offer information about the regulation of immune responses and provide new tools for the therapeutic manipulation of myeloid mononuclear cells in medicine.

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Steady-state MMC homeostasis. (A) Classical mononuclear phagocyte model showing the development of LCs, DCs, and macrophages from a common monocyte precursor.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0015-2015
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Steady-state MMC homeostasis. (B) Current model of DC, monocyte, and macrophage development in which DCs develop through a discrete hematopoietic lineage arising from a bone marrow-resident restricted DC precursor, the CDP. CDPs give rise to pDCs and a myeloid pre-DC population that differentiates into two myeloid DCs (cDC1 and cDC2). It is not known if the pre-DC or cDC1 and cDC2 circulating in the blood give rise to tissue populations of cDC1 and cDC2. Monocytes also contribute to steady-state populations of monocyte-derived macrophages and DCs especially in the skin, gut, and lung. These can be clearly distinguished from the CDP-derived DCs and resident macrophages. Resident macrophages are originally derived from prenatal hematopoiesis. It is unknown whether monocyte-derived cells can contribute to long-term resident macrophages. cMoP, common monocyte progenitor; MAC, macrophage; mo, monocyte.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0015-2015
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Human blood monocytes and DCs. Gating strategy to identify human monocytes and DCs in peripheral blood. Monocytes and DCs are all found in the HLA-DR, lineage-negative compartment. CD14 versus CD16 displays monocyte subsets and double-negative DC populations. These may be separated in a variety of ways. Here the markers CD123 and CD11c are used to define pDCs and myeloid DCs. The latter can be separated into cDC1 and cDC2 using CD141 and CD1c, respectively.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0015-2015
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Summary of human DC, monocyte, and macrophage origins in relation to steady-state surface markers. The most distinctive DC phenotypes are displayed by pDCs and CD141 cDC1 cells. There is more overlap between cDC2 and monocyte-derived cells that may coexist in tissues. Monocyte-derived macrophages also share many markers with resident histiocytes. The relative size of arrows from the precursor populations indicates the estimated steady-state flux. CMoP, common monocyte progenitor; mac, macrophage; mo, monocyte.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0015-2015
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Revised structure of human hematopoiesis showing common lymphomyeloid origin of MMCs including DCs and monocytes. Color coding of progenitor populations is according to their expression of CD38 and CD45RA (inset). B/NK, B- and NK-cell progenitor; EMP, erythromyeloid progenitor; EoBa, eosinophil-basophil progenitor; ETP, early thymic progenitor; GM(D)P, granulocyte-monocyte (DC) progenitor; MEP, mega-erythroid progenitor; MLP, multi-lymphoid progenitor; MDP, monocyte-DC progenitor.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0015-2015
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