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Unravelling mononuclear phagocyte heterogeneity

Nature Reviews Immunology volume 10, pages 453–460 (2010)Cite this article

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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.

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Author information

Authors and Affiliations

  1. Frédéric Geissmann is at King's College London, Guy's Campus, London SE1 1UL, UK. frederic.geissmann@kcl.ac.uk,

    Frédéric Geissmann

  2. Siamon Gordon is at Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK. siamon.gordon@path.ox.ac.uk,

    Siamon Gordon

  3. David A. Hume is at the Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9PS, UK. david.hume@roslin.ed.ac.uk,

    David A. Hume

  4. Allan M. Mowat is at the Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK. a.m.mowat@clinmed.gla.ac.uk,

    Allan M. Mowat

  5. Gwendalyn J. Randolph is at the Mount Sinai School of Medicine, New York, New York 10029, USA. Gwendalyn.Randolph@mssm.edu,

    Gwendalyn J. Randolph

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Glossary

CD11c–DTR (diphtheria toxin receptor) mice

Mice genetically engineered to express the diphtheria toxin receptor under the control of the CD11c promoter. Following administration of diphtheria toxin, cells expressing CD11c are transiently depleted in these animals. These mice have typically been used to study DC function, but certain CD11c+ macrophage populations are also depleted by diphtheria toxin treatment.

Cross-presentation

The mechanism by which certain APCs take up, process and present extracellular antigens on MHC class I molecules to stimulate CD8+ T cells. This property is atypical, as most cells exclusively present peptides derived from endogenous proteins on MHC class I molecules.

Kupffer cell

A specialized macrophage that lines the sinusoidal vessels of the liver. These cells regulate local immune responses, and remove microbial particles, endotoxin and other noxious substances that penetrate the portal venous system.

Langerhans cell

A type of DC that is resident in the epidermal layer of the skin.

M1 macrophages

A macrophage subtype that produces pro-inflammatory cytokines and has cytotoxic functions.

M2 macrophages

A macrophage subtype that acts to dampen inflammatory responses and scavenge debris, as well as to promote angiogenesis and tissue remodelling and repair.

Marginal zone metallophilic macrophage

A type of macrophage that surrounds the splenic white pulp, adjacent to the marginal sinus, and is involved in trapping particulate antigens.

Microglial cell

A phagocytic cell of myeloid origin that is involved in the innate immune response in the central nervous system. Microglial cells are thought to be the brain-resident macrophages.

Mixed leukocyte reaction

(MLR). A tissue-culture technique for testing T cell reactivity and APC activity. A population of T cells is cultured with MHC-mismatched APCs, and proliferation of the T cells is determined by measuring the incorporation of 3H-thymidine into the DNA of dividing cells.

Myeloid-derived suppressor cells

(MDSCs). A group of immature CD11b+GR1+ cells (which include precursors of macrophages, granulocytes, DCs and myeloid cells) that are produced in response to various tumour-derived cytokines. These cells have been shown to induce tumour-associated antigen-specific CD8+ T cell tolerance.

Osteoclast

Multinucleated giant cells, of myeloid origin, that are responsible for bone resorption. Osteoclasts degrade bone matrix and solubilize calcium from bone.

Plasmacytoid DCs

An immature DC with a morphology that resembles that of a plasma cell. Plasmacytoid DCs produce type I IFNs in response to viral infection.

Tumour necrosis factor and inducible nitric oxide synthase-producing DC

(TIP DC). Monocyte-derived DCs that produce high quantities of tumour necrosis factor and nitric oxide. These cells develop in mice from GR1+ monocytes during infection with certain bacteria, such as Listeria monocytogenes, or following myocardial damage.

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Geissmann, F., Gordon, S., Hume, D. et al. Unravelling mononuclear phagocyte heterogeneity. Nat Rev Immunol 10, 453–460 (2010). https://doi.org/10.1038/nri2784

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