Immune Netw.  2015 Aug;15(4):167-176. 10.4110/in.2015.15.4.167.

New Insights Into Tissue Macrophages: From Their Origin to the Development of Memory

• Italiani P
• Boraschi D

• KMID: 2168043
• DOI: http://doi.org/10.4110/in.2015.15.4.167

Abstract

Macrophages are the main effector cells of innate immunity and are involved in inflammatory and anti-infective processes. They also have an essential role in maintaining tissue homeostasis, supporting tissue development, and repairing tissue damage. Until few years ago, it was believed that tissue macrophages derived from circulating blood monocytes, which terminally differentiated in the tissue and unable to proliferate. Recent evidence in the biology of tissue macrophages has uncovered a series of immune and ontogenic features that had been neglected for long, despite old observations. These include origin, heterogeneity, proliferative potential (or self-renewal), polarization, and memory. In recent years, the number of publications on tissue resident macrophages has grown rapidly, highlighting the renewed interest of the immunologists for these key players of innate immunity. This mini-review aims to summarizing the new current knowledge in macrophage immunobiology, in order to offer a clear and immediate overview of the field.

Keyword

Tissue macrophages; Polarization; Innate memory

MeSH Terms

Biology
Homeostasis
Immunity, Innate
Macrophages*
Memory*
Monocytes
Population Characteristics

Figure

• 

  Figure 1 New insights in macrophages. Origin. During embryogenesis, tissue macrophages derive from yolk sac (YS) and fetal liver (FL) progenitors, by primitive and definitive hematopoiesis, respectively. It is possible that FL progenitors may derive from YS progenitors (orange arrow). After birth and in adulthood, monocyte-derived macrophages come from bone marrow (BM) progenitors by definitive hematopoiesis. Heterogeneity/Diversity. Macrophage heterogeneity depends on tissue microenvironment and origin. In the tissue, macrophages can differentiate and acquire a functional specialization depending on tissue-specific signals (▴•♦▪), thereby becoming microglia in the brain, Langerhans cells in the dermis, Kupffer cells in the liver, and gut macrophages (Mϕ) in the intestine. The differentiation in the tissue is both phenotypical and functional, but it is not end-stage, since tissue macrophages retain proliferative/self-renewal capacity and functional plasticity (see below). The yellow and blue bold arrows indicate different origin of these macrophages, being microglia totally yolk sac-derived, while gut macrophages are mostly monocyte-derived macrophages. Thin brown arrows indicate that a fraction of macrophages from FL is already present in tissues such as liver and dermis (taken as examples), but also in peritoneum, lung, spleen, pancreas, and kidney. Polarization/Plasticity. During the different phases of inflammation, the microenviromental changes can polarize macrophages in different functional phenotypes, from an inflammatory (M1) to an alternative/deactivated phenotype (M2), responsible of induction and resolution of inflammation, respectively. These two phenotypes are the extreme of a spectrum of multiple phenotypes (here signed as MX), as many as the microenvironmental scenarios could be. Memory. Macrophages can react to a second challenge reducing (tolerance) or enhancing (trained immunity) their own immune response in terms of cytokine production. Different mechanisms underlie this macrophage capacity, such as epigenetic and metabolic reprogramming or activation of different signaling pathways. In the picture, the memory phenotype referred to as "mixed memory phenotype" indicates that the type of innate memory induced by pre-challenge can be different (increased or decreased cytokine production) and coexist in the same cells depending on the inflammatory cytokines measured and the type of mononuclear phagocyte (see text).

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