The heterogeneity of lung macrophages in the susceptibility to disease

Abstract

Alveolar macrophages are specialised resident phagocytes in the alveolus, constituting the first line of immune cellular defence in the lung. As the lung microenvironment is challenged and remodelled by inhaled pathogens and air particles, so is the alveolar macrophage pool altered by signals that maintain and/or replace its composition. The signals that induce the recruitment of circulating monocytes to the injured lung, as well as their distinct gene expression profile and susceptibility to epigenetic reprogramming by the local environment remain unclear. In this review, we summarise the unique characteristics of the alveolar macrophage pool ontogeny, phenotypic heterogeneity and plasticity during homeostasis, tissue injury and normal ageing. We also discuss new evidence arising from recent studies where investigators described how the epigenetic landscape drives the specific gene expression profile of alveolar macrophages. Altogether, new analysis of macrophages by means of "omic" technologies will allow us to identify key pathways by which these cells contribute to the development and resolution of lung disease in both mice and humans.

FIGURE 1

Lung macrophage development and composition through the lifespan. In the mouse, fetal monocyte cells that populate the lung during early embryogenesis differentiate into alveolar macrophages shortly after birth. This population of “tissue-resident” alveolar macrophages are long-lived and capable of self-renewal in homeostatic conditions (blue line). However, exposure to environmental challenges including viruses, air pollution and cigarette smoke over the lifespan may induce the recruitment of monocytes that differentiate into alveolar macrophages in response to cues provided by the local tissue microenvironment in the lung (red line). Over time, these monocyte-derived alveolar macrophages might persist in the lung and/or replace the tissue-resident alveolar macrophages.