Heterogeneous macrophages: Supersensors of exogenous inducing factors

As heterogeneous immune cells, macrophages mount effective responses to various internal and external changes during disease progression. Macrophage polarization, rather than macrophage heterogenization, is often used to describe the functional differences between macrophages. While macrophage polarization partially contributes to heterogeneity, it does not completely explain the concept of macrophage heterogeneity. At the same time, there are abundant and sophisticated endogenous and exogenous substances that can affect macrophage heterogeneity. While the research on endogenous factors has been systematically reviewed, the findings on exogenous factors have not been well summarized. Hence, we reviewed the characteristics and inducing factors of heterogeneous macrophages to reveal their functional plasticity as well as their targeting manoeuvreability. In the process of constructing and analysing a network organized by disease-related cells and molecules, paying more attention to heterogeneous macrophages as mediators of this network may help to explore a novel entry point for early prevention of and intervention in disease.