Physiological roles of macrophages

Abstract

Macrophages are present in mammals from midgestation, contributing to physiologic homeostasis throughout life. Macrophages arise from yolk sac and foetal liver progenitors during embryonic development in the mouse and persist in different organs as heterogeneous, self-renewing tissue-resident populations. Bone marrow-derived blood monocytes are recruited after birth to replenish tissue-resident populations and to meet further demands during inflammation, infection and metabolic perturbations. Macrophages of mixed origin and different locations vary in replication and turnover, but are all active in mRNA and protein synthesis, fulfilling organ-specific and systemic trophic functions, in addition to host defence. In this review, we emphasise selected properties and non-immune functions of tissue macrophages which contribute to physiologic homeostasis.

Keywords: Homeostasis; Macrophages; Phagocytosis; Physiology; Receptors; Tissue heterogeneity.

Fig. 1

Physiological roles of macrophages and macrophages heterogeneity. Phenotypic heterogeneity of tissue macrophages is triggered by differences in cellular origin (self-replicated cells of embryonic origin vs monocyte-derived), tissue environment and adaptation to the physiological requirements of the organism (shown on the left). Macrophage heterogeneity underpins the vast range of physiological roles performed of these cells (shown on the right). Phenotypic heterogeneity is consolidated by tissue-specific “chromatin landscapes” in macrophages in response to environmental signals. Macrophages display a wide range of “sensor systems” in the form of (a) cell surface and intracellular pattern recognition receptors that detect microbe-associated molecular patterns and damage-associated molecular patterns; (b) receptors for apoptotic cells; (c) cytokine receptors such as IFN-γ and IL-4Rα that promote M1/M2-like activation, respectively; (d) receptors for neurotransmitters as well as (e) receptors that regulate macrophage activation in situ such as the inhibitory receptors SIRP1-α and CD200R. Integrins (f) mediate interaction with extracellular matrix. Macrophages produce numerous molecules that contribute to tissue remodelling and inflammation and mediate clearance of apoptotic bodies, cell debris and soluble compounds such as collagen and lysosomal hydrolases. High phagocytic and endocytic activities as well as motility are central to the ability of macrophages to support tissue-dependent functions. RNS reactive nitrogen species, ROS reactive oxygen species