Abstract
Macrophages are specialized phagocytic cells, present in all tissues, which engulf and digest pathogens, infected and dying cells, and debris, and can recruit and regulate other immune cells and the inflammatory response and aid in tissue repair. Macrophage subpopulations play distinct roles in these processes and in disease, and are typically recognized by differences in marker expression, immune function, or tissue of residency. Although macrophage subpopulations in the brain have been found to have distinct developmental origins, the extent to which development contributes to macrophage diversity between tissues and within tissues is not well understood. Here, we investigate the development and maintenance of mouse lung macrophages by marker expression patterns, genetic lineage tracing and parabiosis. We show that macrophages populate the lung in three developmental waves, each giving rise to a distinct lineage. These lineages express different markers, reside in different locations, renew in different ways, and show little or no interconversion. Thus, development contributes significantly to lung macrophage diversity and targets each lineage to a different anatomical domain.
Highlights
Macrophages are professional phagocytes found in all tissues
Splenic red pulp macrophages remove senescent red blood cells and salvage iron, whereas brain microglia promote neuronal survival (Aguzzi et al, 2013) and lung macrophages catabolize surfactant. Such tissue-specific specializations of macrophages were assumed to be conferred by tissue- and organ-specific microenvironments because all macrophages were thought to arise from a common source: circulating monocytes originating in the bone marrow (Aguzzi et al, 2013; van Furth and Cohn, 1968)
The fetal yolk sac was subsequently identified as another source of macrophages, active before definitive hematopoiesis begins in the fetal liver (Takahashi et al, 1989), Department of Biochemistry and HHMI, Stanford University School of Medicine, Stanford, CA 94305-5307, USA
Summary
Macrophages are professional phagocytes found in all tissues. They are best known for their general functions in clearance of potential pathogens and dead cells, as responders to injury and mediators of inflammation and tissue repair, and for their roles in antigen presentation. Splenic red pulp macrophages remove senescent red blood cells and salvage iron (den Haan and Kraal, 2012), whereas brain microglia promote neuronal survival (Aguzzi et al, 2013) and lung macrophages catabolize surfactant (den Haan and Kraal, 2012; Shibata et al, 2001) Such tissue-specific specializations of macrophages were assumed to be conferred by tissue- and organ-specific microenvironments because all macrophages were thought to arise from a common source: circulating monocytes originating in the bone marrow (Aguzzi et al, 2013; van Furth and Cohn, 1968).
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