The main steps in tissue-resident macrophage ontogeny, as well as the origin of specific macrophage subsets in brain, heart, and aorta, are highlighted below the schematic. Macrophages residing in different organs have diverse gene-expression programs. These cells are highly effective at eating and digesting large particles including dead cells and debris, and microorganisms such as bacteria. During mammary gland development macrophages play a role in controlling proliferation and branching of terminal epithelial buds, in part through CSF-1 and also through expression of chemokine receptors such as CCR2 and D6, which regulate their chemokine levels and recruitment [101]. Intestinal lumen, asterisks. Inflammatory bowel diseases affecting both the small and large intestine promote extensive recruitment of monocytes and activation of macrophages. Cell Rep. 2015;13(9):1937–48. Local macrophages induce tissue-specific metabolic responses such as hepatocyte biosynthesis of plasma proteins that provide an early response to infection in the acute phase reaction, and initiate features of systemic inflammation and infection such as loss of appetite and tissue catabolism [2]. 2016;17(2):159–68. … J Neurosci. They constitute a two-edged sword in host protection and injury, but it is not clear without further study whether their plasticity reflects population changes (recruitment, proliferation versus programmed death, necrosis or emigration) and/or altered gene expression at the level of individual cells. Eur J Immunol. They are Histiocytes (in tissue), Kupffer cells (in liver), Alveolar macrophages (in lungs), Peritoneal macrophages (in peritoneum), Microglial cells (in brain), Mesangial cells (in kidneys) and Osteoclasts (in bone). The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. Bessis M. Erythroblastic island, functional unity of bone marrow. 2014;211(8):1571–83. J Exp Med. SG and AP wrote the article and approved the final manuscript. 4), stromal macrophages at the centre of haematopoietic clusters continue to support the differentiation of erythrocytes and also myeloid leukocytes, including monocytes, by unknown surface and secreted mediators. The origins, differentiation and heterogeneous fate of macrophages are schematically summarised in Fig. Tissue macrophages display remarkable versatility in adapting to the needs of the body, counteracting and limiting changes in their local and systemic environment. Article  Phagocytosis imprints heterogeneity in tissue-resident macrophages. F4/80+ stromal macrophages in the bone marrow play a trophic role in haemopoiesis. These cells together as a group are known as the mononuclear phagocyte system and were previously known as the reticuloendothelial system. In endometrium and placentas, two macrophage subsets were observed: Sn(-)CD163(+) and Sn(+)CD163(+). elife. Morris L, Crocker PR, Gordon S. Murine fetal liver macrophages bind developing erythroblasts by a divalent cation-dependent hemagglutinin. Pathogens Dis. Apart from capturing membrane-bound phosphatidyl serine (PS) + erythrocyte nuclei for digestion, these F4/80+ macrophages bind clusters of developing erythroblasts through a divalent cation-dependent, non-phagocytic receptor selectively expressed by stromal macrophages [42]. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. 2014;182:65–9. 2015;212(9):1433–48. New insights on the role of microglia in synaptic pruning in health and disease. They protect the human body, but they are also involved in the pathogenesis of diseases, including autoimmune disorders, chronic inflammatory syndromes, fibrosis and cancer. In the adult steady state and after sepsis, arterial macrophages are maintained by local proliferation rather than monocyte recruitment. Newsholme P, Gordon S, Newsholme EA. 2017;214(4):1081–92. Therefore, different tissues contain varying mixtures of embryo and marrow-derived macrophages. In the developing brain, macrophages called microglia release CD95L (orange triangles) and other signals that bind the CD95 receptor (blue shapes) on blood vessels and neurons, stimulating them to grow and branch, respectively. Martinez-Pomares L, Gordon S. CD169+ macrophages at the crossroads of antigen presentation. Wilson GJ, Hewit KD, Pallas KJ, Cairney CJ, Lee KM, Hansell CA, Stein T, Graham GJ. Macrophages are derived from three different sources: yolk sac, fetal liver and hematopoietic stem cells in the bone marr… Fate mapping and extensive microarray, enhancer and proteomic analysis established precursor-product relationships and gene expression phenotypes in tissue macrophages ex vivo. 2003;19(1):71–82. Macrophages are present in the anterior and posterior pituitary gland [94, 95], pancreas [96] and adrenal and thyroid glands [97]. Following injury and a range of neurodegenerative diseases, a subset (A1) of neurotoxic reactive astrocytes is induced by activated microglia through secretion of IL-1alpha, TNF and C1q, a component of the classic complement cascade; A1 astrocytes lose their neuronal survival, outgrowth, synaptogenesis and phagocytic activity and induce the death of neurons and oligodendrocytes [78]. Bain CC, Bravo-Blas A, Scott CL, Gomez Perdiguero E. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Immunity. Macrophages are found in almost every organ. In the mouse red pulp, there is also production of monocyte/macrophages which can be recruited to other peripheral organs [48]. Bowman RL, Klemm F, Akkari L, Pyonteck SM, Sevenich L, Quail DF, Dhara S, Simpson K, Gardner EE, Iacobuzio-Donahue CA, et al. Examples. Macrophages provide a first line of defense against microorganisms, and while some mechanisms to kill pathogens such as the oxidative burst are well described, others are still undefined or unknown. As well as responding directly to microorganisms, macrophages are activated by cytokines secreted by the lymphocytes of the adaptive immune system, which, with other environmental immunomodulators, can either direct macrophage differentiation into classic (M1) activation, with enhanced antimicrobial, inflammatory and antigen-presenting properties, or promote an alternative activation phenotype (M2) characterized by anti-inflammatory actions and a distinct set of antimicrobial actions (Additional file 1). The non-classical monocytes patrol the vasculature to clear the damaged endothelial cells (ECs) for maintaining the integrity of endothelium, and thus the vasculature during homeostasis and … J Exp Med. J Am College Cardiol. Microbiol Spectrum. In the peripheral nervous system, macrophages play a major role in myelin phagocytosis and proteolipid breakdown. 2005;23:901–44. Macrophages are known to reside in endocrine glands, and a body … CAS  Recent studies by Squarzoni and colleagues have shown that microglia are able to modulate the outgrowth of dopaminergic neurons in the developing forebrain and the laminar positioning of subsets of neocortical interneurons [72]. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. J Exp Med. Front Physiol. Kupffer cells in the liver; Mesangial cells in the kidney. Platelets, smooth muscle cells, macrophages and fibroblasts all contribute to plaque stability, thromboembolism and plaque rupture. Regional macrophages and related cells were also described in liver (Kupffer cells), lung (alveolar macrophages), and brain (microglia). Interstitial macrophages (IMs) are present in multiple organs. J Leukoc Biol. Most organs contain a heterogeneous mix of bone marrow derived macrophages and macrophages deriving from embryonic progenitors; however, in the brain, the resident macrophage population (microglia) derives solely from the proliferation of progenitors seeded in the embryo. Part of Lepay DA, Steinman RM, Nathan CF, Murray HW, Cohn ZA. 1958;13(1):8–11. 1985;161(6):1503–12. Notably, macrophages are extremely dynamic and highly plastic, as a variety of environmental stimuli alter either the activation status or function of macrophages. Nat Rev Immunol. Intracellular stores can exceed Kupffer cell degradative capacity, resulting in lipid foam cell formation and ferritin accumulation. The adaptation of macrophages and DC to the specialised microenvironment of the intestine is considered in the context of local imprinting by the microbiome, epithelial diversity and lymphocyte heterogeneity by Mucida and colleagues [55]. http://doi.org/10.1084/jem.158.5.1522. Nat Immunol. Tie-2 is an angiopoietin receptor tyrokine kinase implicated in endothelial cell functions, which can also be present on selected macrophages. uncovered that tissue resident macrophages throughout different organs have similar morpho-logical and functional characteristics, suggesting that they share a common progenitor. Infographic: How Vaccines Train innate immunity morris JF, Gordon S. phagocyte! Tissues to perform functions such as tissue repair and inflammation intimate relation endothelium. Cell development Neely H, Whittaker CA, Carr SA, Hynes.. 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