Metchnikoff's policemen: macrophages in development, homeostasis and regeneration

Abstract

Over the past decade, modern genetic tools have permitted scientists to study the function of myeloid lineage cells, including macrophages, as never before. Macrophages were first detected more than a century ago as cells that ingested bacteria and other microbes, but it is now known that their functional roles are far more numerous. In this review, we focus on the prevailing functions of macrophages beyond their role in innate immunity. We highlight examples of macrophages acting as regulators of development, tissue homoeostasis, remodeling (the reorganization or renovation of existing tissues) and repair. We also detail how modern genetic tools have facilitated new insights into these mysterious cells.

Figure 1. Evolution of phagocytosis

The first eukaryotes were formed via endosymbiosis (essentially one bacteria phagocytosing another). Early multi-cellular organisms used phagocytosis to obtain nutrition. Later, these properties were coopted to form an innate immune defense. Eventually, designated phagocytes developed which were cells whose primary purpose was phagocytosis, as apposed to cells that developed the property when necessary.

Figure 2. The broad role of macrophages in development and during repair and regeneration

Macrophages do much more than defend the host from foreign invaders. Macrophages are involved in a host of developmental processes that include determining cell fate (either by affecting what they become or by determining their survival), defining tissue morphogenesis (either directly or indirectly), and by patterning blood vessels. Importantly, many of the properties macrophages use during development are also at work during repair and regeneration. In this context, macrophages can become activated by a host of factors, and then assist in regeneration and/or perform standard immune functions.