Understanding macrophage diversity at the ontogenic and transcriptomic levels

Macrophages are phagocytes characterized by high lysosomal activity and are involved in a wide range of biological processes. Consequently, macrophages have long been recognized for their critical roles in development as well as in healthy and pathological states. Our knowledge about macrophage biology has evolved greatly over the past several years. Significantly, it has now been demonstrated that monocytes are not direct precursors for most tissue-resident macrophages at the steady state. Only few tissue macrophage populations derive from monocytes during homeostasis; rather, monocytes give rise to inflammatory macrophages that infiltrate tissues during inflammation. Tissue-resident macrophages have recently been characterized at the transcriptional level, which provided the basis to uncover the molecular pathways controlling their functional diversity as well as to identify a core signature. Transcription factors controlling specific tissue-resident macrophage populations have been described, suggesting that diversity is under the control of specific regulatory programs. In this review, we discuss and summarize several of the new paradigms emerging in the field of macrophage biology. In particular, we emphasize new findings relevant to macrophage ontogeny, similarities and differences observed across macrophage populations, and gene regulatory programs controlling specialized aspects of tissue macrophage functions.