From drosophila to humans: a journey through macrophage development

Macrophages are fascinating immune cells involved in a variety of processes in both health and disease. Although they were first discovered and characterized by their functions as professional phagocytes and antigen-presenting cells, it is now clear that macrophages have multiple roles within embryonic development, tissue homeostasis, regulation of inflammation, and host response to pathogens and tissue insults. Interestingly, macrophages, or macrophage-like cells, exist in a variety of organisms, from echinoderms to humans, and are present also in species that lack an adaptive immune system or hematopoietic stem cells (HSCs). In mammals, macrophages can be generated from bone marrow precursors through a monocyte intermediate, but it is now known that they are also generated during earlier hematopoietic waves in the embryo. Seeding a variety of tissues at different times, macrophages contribute to embryonic organogenesis and tissue homeostasis. Interestingly, in species where embryonic macrophages are generated before HSC specification, they seem to be an important component of the HSC generative microenvironment. There are many excellent reviews reporting the current knowledge on the ontogeny and functions of macrophages in adult tissues. Here, we aim to summarize the current knowledge on the development and functions of embryonic macrophages across the most used animal models, with a special focus on developmental hematopoiesis.