The role of monocyte-derived macrophages in the lung: It's all about context

Macrophages are present in every tissue of the body where they play crucial roles in maintaining tissue homeostasis and providing front line defence against pathogens. Arguably, this is most important at mucosal barrier tissues, such as the lung and gut, which are major ports of entry for pathogens. However, a common feature of inflammation, infection or injury is the loss of tissue resident macrophages and accumulation of monocytes from the circulation, which differentiate, to different extents, into macrophages. The exact fate and function of these elicited, monocyte-derived macrophages in infection, injury and inflammation remains contentious. While some studies have documented the indispensable nature of monocytes and their macrophage derivatives in combatting infection and restoration of lung homeostasis following insult, observations from clinical studies and preclinical models of lung infection/injury shows that monocytes and their progeny can become dysregulated in severe pathology, often perpetuating rather than resolving the insult. In this review, we aim to bring together these somewhat contradictory reports by discussing how the plasticity of monocytes allow them to assume distinct functions in different contexts in the lung, from health to infection, and effective tissue repair to fibrotic disease.