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Review
. 2015 May 26:6:263.
doi: 10.3389/fimmu.2015.00263. eCollection 2015.

Much More than M1 and M2 Macrophages, There are also CD169(+) and TCR(+) Macrophages

Leslie Chávez-Galán  1 , Maria L Olleros  2 , Dominique Vesin  2 , Irene Garcia  2
Affiliations
Review

Much More than M1 and M2 Macrophages, There are also CD169(+) and TCR(+) Macrophages

Leslie Chávez-Galán et al. Front Immunol. .

Abstract

Monocytes are considered to be precursor cells of the mononuclear phagocytic system, and macrophages are one of the leading members of this cellular system. Macrophages play highly diverse roles in maintaining an organism's integrity by either directly participating in pathogen elimination or repairing tissue under sterile inflammatory conditions. There are different subpopulations of macrophages and each one has its own characteristics and functions. In this review, we summarize present knowledge on the polarization of macrophages that allows the generation of subpopulations called classically activated macrophages or M1 and alternative activated macrophages or M2. Furthermore, there are macrophages that their origin and characterization still remain unclear but have been involved as main players in some human pathologies. Thus, we also review three other categories of macrophages: tumor-associated macrophages, CD169(+) macrophages, and the recently named TCR(+) macrophages. Based on the literature, we provide information on the molecular characterization of these macrophage subpopulations and their specific involvement in several human pathologies such as cancer, infectious diseases, obesity, and asthma. The refined characterization of the macrophage subpopulations can be useful in designing new strategies, supplementing those already established for the treatment of diseases using macrophages as a therapeutic target.

Keywords: M1/M2 polarization; TAM generation; macrophages; monocytes; pathologies.

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Figures

Figure 1
Figure 1
Monocytes are generated in the bone marrow and mobilized to blood and tissue through cytokine signaling to originate macrophage subsets. In the bone marrow, hematopoietic stem cells give rise to MDCP, which divides into two subsets of monocytes, Ly6C+CX3CR1loCCR2+CD62L+ and Ly6CloCX3CR1hiCCR2−CD62L−. Both are mobilized to blood through CCR2 and MCP-3 signaling. Once inside the blood vessels, monocytes are able to leave by extravasation and arrive to tissues via CCR2 and CX3CR1 signaling. A macrophage will originate in a tissue-dependent manner and with its own characteristic and name.
Figure 2
Figure 2
Structure of spleen and lymph node. The spleen has two mayor components, white pulp that includes a central arteriole, T and B cells, and red pulp. Between red and white zone, there is a marginal zone where there are CD169+ macrophages (A). A lymph node is surrounded by a capsule, and the parenchyma is divided into cortex and medulla. The cortex has two zones: outer and inner zone. The subcapsular sinus and medulla zone contain CD169+ macrophages (B).
Figure 3
Figure 3
Molecules associated with macrophage subsets. M1 macrophages, also called classically activated, respond to stimuli such as LPS, IFN-γ, and are important producers of pro-inflammatory cytokines. M2 macrophages, also called alternatively active respond to stimuli such as IL-4 or IL-13, are producer of anti-inflammatory cytokines. Tumor-associated macrophages (TAM) respond to self-tumor microenvironment and secrete cytokines such as TGF-β or IL-10. CD169+ macrophages are involved in immune tolerance and erythropoiesis. TCR+ macrophages are a new subpopulation of macrophages that release chemokine CCL2 and play a role in inflammatory and infectious diseases. Names in black = usually described. Names in white = under specific circumstances can be present in different concentrations.
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