Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny

Abstract

The mononuclear phagocyte system (MPS) has historically been categorized into monocytes, dendritic cells and macrophages on the basis of functional and phenotypical characteristics. However, considering that these characteristics are often overlapping, the distinction between and classification of these cell types has been challenging. In this Opinion article, we propose a unified nomenclature for the MPS. We suggest that these cells can be classified primarily by their ontogeny and secondarily by their location, function and phenotype. We believe that this system permits a more robust classification during both steady-state and inflammatory conditions, with the benefit of spanning different tissues and across species.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A decision tree to facilitate nomenclature decisions for mononuclear phagocytes.
Figure 2: Two levels of nomenclature for classifying mononuclear phagocytes.

Similar content being viewed by others

References

  1. van Furth, R. et al. Mononuclear phagocytic system: new classification of macrophages, monocytes and of their cell line. Bull. World Health Organ. 47, 651–658 (in French) (1972).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Sallusto, F. & Lanzavecchia, A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor-α. J. Exp. Med. 179, 1109–1118 (1994).

    CAS  PubMed  Google Scholar 

  3. Chomarat, P., Banchereau, J., Davoust, J. & Palucka, A. K. IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nature Immunol. 1, 510–514 (2000).

    CAS  Google Scholar 

  4. Metchnikoff, E. Ueber den Kampf der Zellen gegen Erypselkokken, ein Beitrag zur Phagocytenlehre. Arch. Pathol. Anat. [Virchows' Arch.] 107, 209–249 (1887).

    Google Scholar 

  5. Metchnikoff, E. Leçons sur la Pathologie Comparée de l'Inflammation Faites à l'Institut Pasteur en Avril et Mai 1891 (G. Masson, 1892).

    Google Scholar 

  6. Austyn, J. M. & Gordon, S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur. J. Immunol. 11, 805–815 (1981).

    CAS  PubMed  Google Scholar 

  7. Steinman, R. M. & Cohn, Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med. 137, 1142–1162 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Steinman, R. M. & Witmer, M. D. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc. Natl Acad. Sci. USA 75, 5132–5136 (1978).

    CAS  PubMed  Google Scholar 

  9. Metlay, J. P. et al. The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies. J. Exp. Med. 171, 1753–1771 (1990).

    CAS  PubMed  Google Scholar 

  10. Nussenzweig, M. C. et al. Studies of the cell surface of mouse dendritic cells and other leukocytes. J. Exp. Med. 154, 168–187 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Steinman, R. M., Kaplan, G., Witmer, M. D. & Cohn, Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro. J. Exp. Med. 149, 1–16 (1979).

    CAS  PubMed  Google Scholar 

  12. Merad, M., Sathe, P., Helft, J., Miller, J. & Mortha, A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu. Rev. Immunol. 31, 563–604 (2013).

    CAS  PubMed  Google Scholar 

  13. Ginhoux, F. & Jung, S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nature Rev. Immunol. 14, 392–404 (2014).

    CAS  Google Scholar 

  14. Mildner, A. & Jung, S. Development and function of dendritic cell subsets. Immunity 40, 642–656 (2014).

    CAS  PubMed  Google Scholar 

  15. Hume, D. A. Macrophages as APC and the dendritic cell myth. J. Immunol. 181, 5829–5835 (2008).

    CAS  PubMed  Google Scholar 

  16. Varol, C. et al. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31, 502–512 (2009).

    CAS  PubMed  Google Scholar 

  17. Bogunovic, M. et al. Origin of the lamina propria dendritic cell network. Immunity 31, 513–525 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Bain, C. C. & Mowat, A. M. The monocyte-macrophage axis in the intestine. Cell. Immunol. http://dx.doi.org/10.1016/j.cellimm.2014.03.012 (2014).

    Google Scholar 

  19. Kim, K. W. et al. In vivo structure/function and expression analysis of the CX3C chemokine fractalkine. Blood 118, e156–e167 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Rescigno, M. et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature Immunol. 2, 361–367 (2001).

    CAS  Google Scholar 

  21. Serbina, N. V., Salazar-Mather, T. P., Biron, C. A., Kuziel, W. A. & Pamer, E. G. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19, 59–70 (2003).

    CAS  PubMed  Google Scholar 

  22. Dunay, I. R. et al. Gr1+ inflammatory monocytes are required for mucosal resistance to the pathogen Toxoplasma gondii. Immunity 29, 306–317 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Tamoutounour, S. et al. CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis. Eur. J. Immunol. 42, 3150–3166 (2012).

    CAS  PubMed  Google Scholar 

  24. Schulz, C. et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336, 86–90 (2012).

    CAS  PubMed  Google Scholar 

  25. Yona, S. et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79–91 (2013).

    CAS  PubMed  Google Scholar 

  26. Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Naito, M., Hasegawa, G. & Takahashi, K. Development, differentiation, and maturation of Kupffer cells. Microsc. Res. Tech. 39, 350–364 (1997).

    CAS  PubMed  Google Scholar 

  28. Yamada, M., Naito, M. & Takahashi, K. Kupffer cell proliferation and glucan-induced granuloma formation in mice depleted of blood monocytes by strontium-89. J. Leukoc. Biol. 47, 195–205 (1990).

    CAS  PubMed  Google Scholar 

  29. Alliot, F., Godin, I. & Pessac, B. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res. Dev. Brain Res. 117, 145–152 (1999).

    CAS  PubMed  Google Scholar 

  30. Guilliams, M. et al. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J. Exp. Med. 210, 1977–1992 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Hettinger, J. et al. Origin of monocytes and macrophages in a committed progenitor. Nature Immunol. 14, 821–830 (2013).

    CAS  Google Scholar 

  32. Jakubzick, C. et al. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39, 599–610 (2013).

    CAS  PubMed  Google Scholar 

  33. Tamoutounour, S. et al. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39, 925–938 (2013).

    CAS  PubMed  Google Scholar 

  34. Avraham-Davidi, I. et al. On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells. J. Exp. Med. 210, 2611–2625 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Naik, S. H. et al. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nature Immunol. 8, 1217–1226 (2007).

    CAS  Google Scholar 

  36. Onai, N. et al. Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nature Immunol. 8, 1207–1216 (2007).

    CAS  Google Scholar 

  37. Ziegler-Heitbrock, L. et al. Nomenclature of monocytes and dendritic cells in blood. Blood 116, e74–e80 (2010).

    CAS  PubMed  Google Scholar 

  38. Rissoan, M. C. et al. Reciprocal control of T helper cell and dendritic cell differentiation. Science 283, 1183–1186 (1999).

    CAS  PubMed  Google Scholar 

  39. Vremec, D. & Shortman, K. Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. J. Immunol. 159, 565–573 (1997).

    CAS  PubMed  Google Scholar 

  40. Meredith, M. M. et al. Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage. J. Exp. Med. 209, 1153–1165 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Persson, E. K. et al. IRF4 transcription-factor-dependent CD103+CD11b+ dendritic cells drive mucosal T helper 17 cell differentiation. Immunity 38, 958–969 (2013).

    CAS  PubMed  Google Scholar 

  42. Schlitzer, A. et al. IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity 38, 970–983 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Mashayekhi, M. et al. CD8α+ dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity 35, 249–259 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Plantinga, M. et al. Conventional and monocyte-derived CD11b+ dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. Immunity 38, 322–335 (2013).

    CAS  PubMed  Google Scholar 

  45. Desch, A. N. et al. CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic cell-associated antigen. J. Exp. Med. 208, 1789–1797 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Naik, S. H. et al. Diverse and heritable lineage imprinting of early haematopoietic progenitors. Nature 496, 229–232 (2013).

    CAS  PubMed  Google Scholar 

  47. Schraml, B. U. et al. Genetic tracing via DNGR-1 expression history defines dendritic cells as a hematopoietic lineage. Cell 154, 843–858 (2013).

    CAS  PubMed  Google Scholar 

  48. Onai, N. et al. A clonogenic progenitor with prominent plasmacytoid dendritic cell developmental potential. Immunity 38, 943–957 (2013).

    CAS  PubMed  Google Scholar 

  49. Naik, S. H. et al. Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nature Immunol. 7, 663–671 (2006).

    CAS  Google Scholar 

  50. Diao, J., Winter, E., Chen, W., Cantin, C. & Cattral, M. S. Characterization of distinct conventional and plasmacytoid dendritic cell-committed precursors in murine bone marrow. J. Immunol. 173, 1826–1833 (2004).

    CAS  PubMed  Google Scholar 

  51. Liu, K. et al. In vivo analysis of dendritic cell development and homeostasis. Science 324, 392–397 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Toyama-Sorimachi, N. et al. Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependent manner. J. Immunol. 174, 4621–4629 (2005).

    CAS  PubMed  Google Scholar 

  53. Jackson, J. T. et al. Id2 expression delineates differential checkpoints in the genetic program of CD8α+ and CD103+ dendritic cell lineages. EMBO J. 30, 2690–2704 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Corcoran, L. et al. The lymphoid past of mouse plasmacytoid cells and thymic dendritic cells. J. Immunol. 170, 4926–4932 (2003).

    CAS  PubMed  Google Scholar 

  55. Pelayo, R. et al. Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow. Blood 105, 4407–4415 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. McKenna, H. J. et al. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 95, 3489–3497 (2000).

    CAS  PubMed  Google Scholar 

  57. Waskow, C. et al. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nature Immunol. 9, 676–683 (2008).

    CAS  Google Scholar 

  58. Ginhoux, F. et al. The origin and development of nonlymphoid tissue CD103+ DCs. J. Exp. Med. 206, 3115–3130 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Schiavoni, G. et al. ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8α+ dendritic cells. J. Exp. Med. 196, 1415–1425 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Hacker, C. et al. Transcriptional profiling identifies Id2 function in dendritic cell development. Nature Immunol. 4, 380–386 (2003).

    CAS  Google Scholar 

  61. Hildner, K. et al. Batf3 deficiency reveals a critical role for CD8α+ dendritic cells in cytotoxic T cell immunity. Science 322, 1097–1100 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Kashiwada, M., Pham, N. L., Pewe, L. L., Harty, J. T. & Rothman, P. B. NFIL3/E4BP4 is a key transcription factor for CD8α+ dendritic cell development. Blood 117, 6193–6197 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Wu, L. et al. RelB is essential for the development of myeloid-related CD8α- dendritic cells but not of lymphoid-related CD8α+ dendritic cells. Immunity 9, 839–847 (1998).

    CAS  PubMed  Google Scholar 

  64. Guerriero, A., Langmuir, P. B., Spain, L. M. & Scott, E. W. PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells. Blood 95, 879–885 (2000).

    CAS  PubMed  Google Scholar 

  65. Caton, M. L., Smith-Raska, M. R. & Reizis, B. Notch-RBP-J signaling controls the homeostasis of CD8 dendritic cells in the spleen. J. Exp. Med. 204, 1653–1664 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Lewis, K. L. et al. Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine. Immunity 35, 780–791 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Satpathy, A. T. et al. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nature Immunol. 14, 937–948 (2013).

    CAS  Google Scholar 

  68. Suzuki, S. et al. Critical roles of interferon regulatory factor 4 in CD11bhighCD8α dendritic cell development. Proc. Natl Acad. Sci. USA 101, 8981–8986 (2004).

    CAS  PubMed  Google Scholar 

  69. Tamura, T. et al. IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity. J. Immunol. 174, 2573–2581 (2005).

    CAS  PubMed  Google Scholar 

  70. Seillet, C. et al. CD8α+ DCs can be induced in the absence of transcription factors Id2, Nfil3, and Batf3. Blood 121, 1574–1583 (2013).

    CAS  PubMed  Google Scholar 

  71. Ghosh, H. S., Cisse, B., Bunin, A., Lewis, K. L. & Reizis, B. Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity 33, 905–916 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Cisse, B. et al. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135, 37–48 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Hoeffel, G. et al. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J. Exp. Med. 209, 1167–1181 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Zigmond, E. et al. Infiltrating monocyte-derived macrophages and resident Kupffer cells display different ontogeny and functions in acute liver injury. J. Immunol. 193, 344–353 (2014).

    CAS  PubMed  Google Scholar 

  75. Greter, M. et al. Stroma-derived interleukin-34 controls the development and maintenance of Langerhans cells and the maintenance of microglia. Immunity 37, 1050–1060 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Wang, Y. et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nature Immunol. 13, 753–760 (2012).

    CAS  Google Scholar 

  77. Gautier, E. L. et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nature Immunol. 13, 1118–1128 (2012).

    CAS  Google Scholar 

  78. Rosas, M. et al. The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal. Science 344, 645–648 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Okabe, Y. & Medzhitov, R. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 157, 832–844 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Geissmann, F., Jung, S. & Littman, D. R. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19, 71–82 (2003).

    CAS  PubMed  Google Scholar 

  81. Swirski, F. K. et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325, 612–616 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Auffray, C. et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317, 666–670 (2007).

    CAS  PubMed  Google Scholar 

  83. Sunderkotter, C. et al. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J. Immunol. 172, 4410–4417 (2004).

    PubMed  Google Scholar 

  84. Varol, C. et al. Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J. Exp. Med. 204, 171–180 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Epelman, S. et al. Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40, 91–104 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Arnold, L. et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J. Exp. Med. 204, 1057–1069 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Mildner, A. et al. CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain 132, 2487–2500 (2009).

    PubMed  Google Scholar 

  88. Kool, M. et al. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J. Exp. Med. 205, 869–882 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Cheong, C. et al. Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209+ dendritic cells for immune T cell areas. Cell 143, 416–429 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Langlet, C. et al. CD64 expression distinguishes monocyte-derived and conventional dendritic cells and reveals their distinct role during intramuscular immunization. J. Immunol. 188, 1751–1760 (2012).

    CAS  PubMed  Google Scholar 

  91. Xu, Y., Zhan, Y., Lew, A. M., Naik, S. H. & Kershaw, M. H. Differential development of murine dendritic cells by GM-CSF versus Flt3 ligand has implications for inflammation and trafficking. J. Immunol. 179, 7577–7584 (2007).

    CAS  PubMed  Google Scholar 

  92. Robbins, S. H. et al. Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling. Genome Biol. 9, R17 (2008).

    PubMed  PubMed Central  Google Scholar 

  93. Crozat, K. et al. Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets. Immunol. Rev. 234, 177–198 (2010).

    CAS  PubMed  Google Scholar 

  94. Guilliams, M. et al. From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets. Eur. J. Immunol. 40, 2089–2094 (2010).

    CAS  PubMed  Google Scholar 

  95. Fairbairn, L. et al. Comparative analysis of monocyte subsets in the pig. J. Immunol. 190, 6389–6396 (2013).

    CAS  PubMed  Google Scholar 

  96. Chamorro, S. et al. Phenotypic characterization of monocyte subpopulations in the pig. Immunobiology 202, 82–93 (2000).

    CAS  PubMed  Google Scholar 

  97. Contreras, V. et al. Existence of CD8α-like dendritic cells with a conserved functional specialization and a common molecular signature in distant mammalian species. J. Immunol. 185, 3313–3325 (2010).

    CAS  PubMed  Google Scholar 

  98. Marquet, F. et al. Characterization of dendritic cells subpopulations in skin and afferent lymph in the swine model. PLoS ONE 6, e16320 (2011).

    PubMed  PubMed Central  Google Scholar 

  99. Vu Manh, T. P. et al. Existence of conventional dendritic cells in Gallus gallus revealed by comparative gene expression profiling. J. Immunol. 192, 4510–4517 (2014).

    CAS  PubMed  Google Scholar 

  100. Dutertre, C. A. et al. TLR3-responsive, XCR1+, CD141(BDCA-3)+/CD8α+-equivalent dendritic cells uncovered in healthy and simian immunodeficiency virus-infected rhesus macaques. J. Immunol. 192, 4697–4708 (2014).

    CAS  PubMed  Google Scholar 

  101. Segura, E. et al. Characterization of resident and migratory dendritic cells in human lymph nodes. J. Exp. Med. 209, 653–660 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Summers, K. L., Hock, B. D., McKenzie, J. L. & Hart, D. N. Phenotypic characterization of five dendritic cell subsets in human tonsils. Am. J. Pathol. 159, 285–295 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. McIlroy, D. et al. Investigation of human spleen dendritic cell phenotype and distribution reveals evidence of in vivo activation in a subset of organ donors. Blood 97, 3470–3477 (2001).

    CAS  PubMed  Google Scholar 

  104. Haniffa, M. et al. Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity 37, 60–73 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Yu, C. I. et al. Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal effector t cells via the cytokine TGF-β. Immunity 38, 818–830 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Jongbloed, S. L. et al. Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J. Exp. Med. 207, 1247–1260 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Crozat, K. et al. The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells. J. Exp. Med. 207, 1283–1292 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Bachem, A. et al. Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J. Exp. Med. 207, 1273–1281 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Poulin, L. F. et al. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells. J. Exp. Med. 207, 1261–1271 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Galibert, L. et al. Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated molecule. J. Biol. Chem. 280, 21955–21964 (2005).

    CAS  PubMed  Google Scholar 

  111. Pulendran, B. et al. Flt3-ligand and granulocyte colony-stimulating factor mobilize distinct human dendritic cell subsets in vivo. J. Immunol. 165, 566–572 (2000).

    CAS  PubMed  Google Scholar 

  112. Poulin, L. F. et al. DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and non-lymphoid tissues. Blood 119, 6052–6062 (2012).

    CAS  PubMed  Google Scholar 

  113. Watchmaker, P. B. et al. Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice. Nature Immunol. 15, 98–108 (2014).

    CAS  Google Scholar 

  114. Haniffa, M. et al. Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation. J. Exp. Med. 206, 371–385 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Bigley, V. et al. The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. J. Exp. Med. 208, 227–234 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Kanitakis, J., Morelon, E., Petruzzo, P., Badet, L. & Dubernard, J. M. Self-renewal capacity of human epidermal Langerhans cells: observations made on a composite tissue allograft. Exp. Dermatol. 20, 145–146 (2011).

    CAS  PubMed  Google Scholar 

  117. Cros, J. et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 33, 375–386 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Ingersoll, M. A. et al. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 115, e10–e19 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Segura, E. et al. Human inflammatory dendritic cells induce Th17 cell differentiation. Immunity 38, 336–348 (2013).

    CAS  PubMed  Google Scholar 

  120. Guttman-Yassky, E. et al. Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis. J. Allergy Clin. Immunol. 119, 1210–1217 (2007).

    CAS  PubMed  Google Scholar 

  121. Nakano, H., Yanagita, M. & Gunn, M. D. CD11c+B220+Gr-1+ cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells. J. Exp. Med. 194, 1171–1178 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Lauterbach, H. et al. Mouse CD8α+ DCs and human BDCA3+ DCs are major producers of IFN-λ in response to poly IC. J. Exp. Med. 207, 2703–2717 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Nizzoli, G. et al. Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T cell responses. Blood 122, 932–942 (2013).

    CAS  PubMed  Google Scholar 

  124. Segura, E. & Amigorena, S. Cross-presentation by human dendritic cell subsets. Immunol. Lett. 158, 73–78 (2014).

    CAS  PubMed  Google Scholar 

  125. Tauber, A. & Chernyak, L. Metchnikoff and the Origins of Immunology: From Metaphor to Theory (Oxford Univ. Press, 1991).

    Google Scholar 

  126. Gordon, S. Elie Metchnikoff: father of natural immunity. Eur. J. Immunol. 38, 3257–3264 (2008).

    CAS  PubMed  Google Scholar 

  127. Florey, H. General Pathology (Lloyd-Luke, 1970).

    Google Scholar 

  128. Aschoff, L. Das reticuloendotheliale System. Erg. Inn. Med. Kinderheilk. 26, 1–118 (1924).

    Google Scholar 

  129. Carrel, A. & Ebeling, A. H. The fundamental properties of the fibroblast and the macrophage: II. the macrophage. J. Exp. Med. 44, 285–305 (1926).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Awrorow, P. P. & Timofejewskij, A. D. in Virchows Archiv Fur Pathologische Anatomie Und Physiologie Und Fur Klinische Medizin. Vol. 216, 184–214 (Springer, 1914).

    Google Scholar 

  131. Lewis, M. R. & Lewis, W. H. The transformation of white blood cells into clasmatocytes (macrophages), epithelioid cells, and giant cells. J. Am. Med. Associ. 84, 798–799 (1925).

    Google Scholar 

  132. Ebert, R. H. & Florey, H. W. The extravascular development of the monocyte observed in vivo. Br. J. Exp. Pathol. 20, 342–356 (1939).

    PubMed Central  Google Scholar 

  133. Volkman, A. & Gowans, J. L. The origin of macrophages from bone marrow in the rat. Br. J. Exp. Pathol. 46, 62–70 (1965).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Gall, E. A. The cytological identity and interrelation of mesenchymal cells of lymphoid tissue. Ann. NY Acad. Sci. 73, 120–130 (1958).

    CAS  PubMed  Google Scholar 

  135. Ratcliffe, N. A. & Rowley, A. F. Invertebrate Blood Cells (Academic Press, 1981).

    Google Scholar 

  136. George, W. C. Comparative hematology and the functions of the leucocytes. Quarterly Rev. Biol. 16, 426–439 (1941).

    Google Scholar 

  137. Maximow, A. Uber die Entwicklung der blut - und Bindegewebszellen beim Saugetierembryo. Folia Haematol. 4, 16 (1907).

    Google Scholar 

  138. Mosier, D. E. & Coppleson, L. W. A three-cell interaction required for the induction of the primary immune response in vitro. Proc. Natl Acad. Sci. USA 61, 542–547 (1968).

    CAS  PubMed  Google Scholar 

  139. van Furth, R. in Methods for Studying Mononuclear Phagocytes (eds Adams, D. O., Edelson, P. J. & Koren, H.) 243–252 (Academic Press, 1980).

    Google Scholar 

  140. Foucar, K. & Foucar, E. The mononuclear phagocyte and immunoregulatory effector (M-PIRE) system: evolving concepts. Semin. Diagn. Pathol. 7, 4–18 (1990).

    CAS  PubMed  Google Scholar 

  141. Goerdt, S., Kodelja, V., Schmuth, M., Orfanos, C. E. & Sorg, C. The mononuclear phagocyte-dendritic cell dichotomy: myths, facts, and a revised concept. Clin. Exp. Immunol. 105, 1–9 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Hashimoto, D. et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38, 792–804 (2013).

    CAS  PubMed  Google Scholar 

  143. Witmer-Pack, M. D. et al. Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse. J. Cell Sci. 104, 1021–1029 (1993).

    PubMed  Google Scholar 

  144. Hilgendorf, I. et al. Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ. Res. 114, 1611–1622 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The opinions presented here are solely those of the authors but during the course of writing this piece, invaluable guidance and advice was sought from S. Jung, K. Shortman, K. Murphy, S. Gordon, A. Mowat, G. Randolph, C. Reis e Sousa, S. Amigorena, B. Malissen, T. Ohteki, P. Henson, D. Riches, M. Merad, M. Manz, M. Dalod, S. Henri, B. Lambrecht, C. Scott, L. van de Laar, D. Metcalf, S. Zelenay and P. Whitney. The authors also thank M. Haniffa for reviewing the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Martin Guilliams, Florent Ginhoux, Claudia Jakubzick, Shalin H. Naik, Nobuyuki Onai, Barbara U. Schraml, Elodie Segura, Roxane Tussiwand or Simon Yona.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information S1 (table)

Mouse mononuclear phagocytes (PDF 162 kb)

Supplementary information S2 (table)

Human mononuclear phagocytes (PDF 161 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guilliams, M., Ginhoux, F., Jakubzick, C. et al. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol 14, 571–578 (2014). https://doi.org/10.1038/nri3712

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri3712

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing