Diversity, Mechanisms, and Significance of Macrophage Plasticity

Abstract

Macrophages are a diverse set of cells present in all body compartments. This diversity is imprinted by their ontogenetic origin (embryonal versus adult bone marrow-derived cells); the organ context; by their activation or deactivation by various signals in the contexts of microbial invasion, tissue damage, and metabolic derangement; and by polarization of adaptive T cell responses. Classic adaptive responses of macrophages include tolerance, priming, and a wide spectrum of activation states, including M1, M2, or M2-like. Moreover, macrophages can retain long-term imprinting of microbial encounters (trained innate immunity). Single-cell analysis of mononuclear phagocytes in health and disease has added a new dimension to our understanding of the diversity of macrophage differentiation and activation. Epigenetic landscapes, transcription factors, and microRNA networks underlie the adaptability of macrophages to different environmental cues. Macrophage plasticity, an essential component of chronic inflammation, and its involvement in diverse human diseases, most notably cancer, is discussed here as a paradigm.

Keywords: cancer; checkpoints; epigenetics; macrophages; microRNA; plasticity.

Figure 1

Homeostatic functions of macrophages (A) and response to environmental perturbations (B) to restore homeostasis. Selected organs or tissues and homeostatic functions are presented. R stands for receptor.

Figure 2

Chromatin modifications underlying priming, tolerance and training.

Figure 3

MicroRNAs in the regulation of macrophage plasticity.

Figure 4

Macrophages as double edged swords in the regulation of tumor progression and response aa, aminoacid, PG, prostaglandins (A) and general response to perturbation (B).