What is the difference between dendritic cells and macrophages

Researchers from both, the DC and the macrophage fields, have investigated kidney mononuclear phagocytes defined by cell surface markers in homeostasis and models of renal disease. Many important roles were shown in models of acute renal injury and in chronic immune-mediated kidney disease Table 1 , such as cytokine production or T cell-crosstalk in response to tissue injury or infection 17 , 25 — However, none of these functions is generally accepted to be exclusive for DCs or macrophages.

Also, the tools used for loss-of-function studies cannot clearly discriminate between DCs and macrophages: CD11c—DTR mice are used to deplete kidney DCs, CD11b—DTR mice for depleting kidney macrophages but the expression of CD11c and CD11b on kidney mononuclear phagocytes is too heterogeneous for this black-and-white thinking Clodronate liposomes are used for both purposes 35 — All kidney mononuclear phagocytes are phagocytic 34 which might render them sensitive to clodronate liposomes.

Table 1. The consequence of this overlap is well illustrated by two recent studies examining how CX 3 CR1 affects renal disease: both studies agreed that mononuclear phagocytes are substantially reduced in the kidneys of CX 3 CR1-deficient mice. However, one of them noted a higher susceptibility to renal candidiasis and attributed this to the loss of renal macrophages 19 , while the other documented protection against glomerulonephritis and assigned this to the loss of renal DCs A possible explanation for this different classifications is that glomerulonephritis is driven mostly by phagocytes in the kidney cortex, in which glomeruli are located, whereas anti-infectious activity seem to be primarily due to phagocytes in the medulla, through which pathogens enter the kidney Medullary phagocytes express significantly less CD11c than those in the cortex, which may bias their classification as DCs.

The causes for these phenotypical and functional differences between medullary and cortical mononuclear phagocytes are unknown, but may result from differences in osmolarity, pH, and oxygen tension between these compartments, to which the mononuclear phagocytes may adapt. This would be in line with the current view that the tissue microenvironment dictates the organ-specific plasticity of macrophages 39 , 40 , and thus, perhaps also of renal mononuclear phagocytes.

The current definitions of renal DCs and macrophages are not mutually exclusive, so that renal mononuclear phagocytes may fulfill the definitions of both cell types simultaneously. This creates confusion, especially among those nephrologists that are more interested in disease relevance than in semantics. This classification was based on the following facts: 1 most adult macrophages in tissues are successors of an embryonic precursor and maintained through self-renewal 42 — 46 , 2 a common monocyte progenitor cMoP exists, which gives rise to monocytes 47 , and 3 conventional DC cDC and plasmacytoid DC but not monocytes or macrophages arise from a common DC precursor CDP 48 , Finally, monocyte-derived cells differentiate from cMoP that can exert macrophage- or DC-like functions and express markers associated with either This classification does not resolve the question whether monocyte-derived macrophages and monocyte-derived DCs are ontogenically distinct or whether one cell type displays high plasticity in different microenvironments.

While this nomenclature proposal might bring order into the ever increasing numbers DC and macrophage subsets, one major concern remains: without fate mapping tools, the origin of a phagocyte in a given tissue is usually not apparent, so that surrogate markers need to be used.

Several markers for distinguishing phagocytes derived from different precursors are currently being discussed, but as we shall see below, they fail to discriminate renal DCs and macrophages. One of these markers, CD64, alone or in combination with CCR2 or MerTK, has been reported to identify monocyte-derived macrophages and to be able to discriminate DC from non-DC in the intestine, the muscle and spleen 52 — 55 , and the skin DNGR1, when combined with genetic fate mapping technology, was shown to mark CDP and pre-DC 51 , whereas Csf1r can be used for fate mapping of yolk sac derived myb independent tissue macrophages Similarly, another fate mapping study that used Myb and PU.

These findings highlight the difficulties when basing cellular classification solely on ontogeny when ontogeny is based on surrogate markers. Furthermore, transferring ontogeny-based nomenclature to human mononuclear phagocytes in tissue might prove impracticable.

However, these constitute the vast majority of kidney mononuclear phagocytes. Another classification approach is based on mononuclear phagocyte functionality. However, observed functions generally represent a snapshot of a cell within a specific context and time frame. Demonstrating that a phagocyte performs a given function under certain conditions at a certain time-point does not imply that this is a general feature of this cell.

Furthermore, there is no clear demarcation between exclusive DC and macrophage functions. For example, macrophages phagocytose and degrade material.

However, under certain conditions DCs do that too, albeit less efficiently [reviewed in Ref. Furthermore, the ability to stimulate T cells is difficult to determine on a single cell basis. A recent study differentiated renal mononuclear phagocytes into five phenotypically and functionally distinct populations Functional analyses and fate mapping studies were used for further characterization.

In line with the complexity of kidney mononuclear phagocyte subsets observed by others and us 17 , 45 , 51 , the study revealed that all subsets expressed CD68 that is usually used to identify macrophages and that all subsets were phagocytic but showed differences in their antigen presentation capacity.

Fate mapping experiments identified one population with a dual origin, two populations that were closely related to monocytes, whereas the remaining two were not. Notably, the largest population not only showed the phenotypical and functional characteristics of reparative macrophages M2 but also had significant antigen presentation function and most likely emigrated from the kidney under inflammatory conditions.

Additionally, this population differed significantly between mouse strains, which might explain immunological differences between those strains. The authors concluded that functions are more related to context than separate lineage and suggested their marker combination as an unbiased approach to identify kidney mononuclear phagocyte populations These findings are consistent with recent concepts that macrophage fine differentiation is shaped by the tissue microenvironment 39 , As a consequence of the separate development of the DC and macrophage research communities, the functional and phenotypic definitions of these cell types overlap substantially.

Thus, scientists from both communities often study the same cells, perhaps unaware of, or ignoring progress and concepts in the other field. The false assumption that classifying a mononuclear phagocyte as a macrophage implies that it is not a DC, and vice versa, hampers communication between researchers from both fields.

This may result in highly citable or controversial publications, but it does not advance our understanding of mononuclear phagocytes, neither in the kidney nor elsewhere. An overlapping classification system, such as the existing one, is certainly not desirable. An improvement is needed. It is unrealistic to assume that either the DC or the macrophage community will accept the nomenclature of the other field. Drawing a line that segregates mononuclear phagocytes into DCs or macrophages will unlikely be acceptable to both fields.

Furthermore, there are currently no unambiguous discriminatory parameters; for any new parameters introduced, exceptions are reported quickly, such as for CD64 and DNGR1-fate tracking in the kidney. Still, an improved classification system is needed. How can we reach a consensus?

First, the purpose of the revised classification system needs to be defined. Clinicians are interested in cellular entities that are useful for diagnostic or therapeutic purposes and translational immunologists often study the functions of cellular subsets. Basic immunologists may favor ontogeny, which is biologically the cleanest and most logical approach.

However, mononuclear phagocytes adapt their gene enhancer landscape according to the tissue of residence independently of the precursor they originated from 39 , an ontogeny-based nomenclature may lead to different cell types with similar functionality, or to cells of the same name with different functionality depending on the organ they reside in.

Moreover, the origin of a mononuclear phagocyte in a given tissue is not obviously apparent, because unique discriminatory parameters are missing. Thus, ontogeny, although theoretically logical, will be difficult to use for routine research.

At the end of the day, a classification system needs to be convenient and feasible, or it will not be used. Indeed, at the age of single cell transcriptomics, it becomes clear that several transcriptional programs may run simultaneously in individual mononuclear phagocytes, and confer a spectrum of functionalities that are more or less consistent with the current concepts of a DC, of a macrophage, or both.

Current technical advances will undoubtedly allow distinguishing far more functional states of mononuclear phagocytes. It remains to be seen whether basic immunologists and scientists studying mononuclear phagocytes in other organs feel that this is useful or not. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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J Exp Med 2 — Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9 — Dendritic cell and macrophage heterogeneity in vivo. Immunity 35 3 — Saba TM. Physiology and physiopathology of the reticuloendothelial system. The activation of the dendritic cells mainly occurs through the inflammatory cytokines secreted by macrophages. Once activated by a particular inflammatory stimulus, dendritic cells cannot take up a second stimulus and they become efficient antigen-processing cells.

The activated dendritic cells migrate to the T cell areas in the secondary lymphoid organs to present the processed antigens to the naive T cells. More significantly, after achieving the effector function, dendritic cells undergo terminal differentiation and die via apoptosis.

Macrophages refer to a type of white blood cells that surround and kill microorganisms, remove dead cells, and stimulate the activity of other immune system cells. Dendritic cells refer to a special type of immune cells that boost immune responses by showing antigens on its surface to other cells of the immune system.

Therefore, these definitions explain the important difference between macrophages and dendritic cells. There is also a difference between macrophages and dendritic cells based on their location. Macrophages occur in the stationary form in tissues or as a mobile white blood cell, especially at sites of infection while dendritic cells occur in tissues, such as the skin. Another difference between macrophages and dendritic cells is that macrophages initiate the inflammatory process in tissues while dendritic cells activate upon inflammatory signals.

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Download references. The authors thank M. Dalod, M. Guilliams, A. Mowat, H. Luche and D. Terhorst for their helpful discussions. You can also search for this author in PubMed Google Scholar. Correspondence to Bernard Malissen.

Hapten-specific T cell-mediated skin inflammation that is induced by painting a hapten onto the skin. During the sensitization phase, hapten-bearing skin dendritic cells migrate to the lymph nodes where they induce hapten-specific T cells. Re-exposure to the same hapten results in the activation of the specific T cells in the dermis, which triggers the inflammatory process that is responsible for the cutaneous lesion.

Some cells contain molecules that become fluorescent when excited by radiation of suitable wavelength. This autofluorescence arises from endogenous fluorophores and differs from fluorescent signals that are obtained after adding antibodies that are conjugated to fluorophores. A solution prepared from non-metabolizable oils that is the most commonly used adjuvant in research. Reprints and Permissions. Malissen, B. The origins and functions of dendritic cells and macrophages in the skin.

Nat Rev Immunol 14, — Download citation. Published : 23 May Issue Date : June Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Nature Communications BioDrugs Seminars in Immunopathology Advanced search. Skip to main content Thank you for visiting nature. Subjects Antigen presentation Dendritic cells Monocytes and macrophages.

Abstract Immune cell populations in the skin are predominantly comprised of dendritic cells DCs and macrophages. Access through your institution. Buy or subscribe. Rent or Buy article Get time limited or full article access on ReadCube.

Figure 1: Antigen-presenting cell populations of the healthy skin. Figure 2: Subsets of skin dendritic cells and macrophages. Figure 3: Origin of dermal macrophages.