Diversity of Macrophages in Lung Homeostasis and Diseases

Abstract

Lung macrophages play important roles in the maintenance of homeostasis, pathogen clearance and immune regulation. The different types of pulmonary macrophages and their roles in lung diseases have attracted attention in recent years. Alveolar macrophages (AMs), including tissue-resident alveolar macrophages (TR-AMs) and monocyte-derived alveolar macrophages (Mo-AMs), as well as interstitial macrophages (IMs) are the major macrophage populations in the lung and have unique characteristics in both steady-state conditions and disease states. The different characteristics of these three types of macrophages determine the different roles they play in the development of disease. Therefore, it is important to fully understand the similarities and differences among these three types of macrophages for the study of lung diseases. In this review, we will discuss the physiological characteristics and unique functions of these three types of macrophages in acute and chronic lung diseases. We will also discuss possible methods to target macrophages in lung diseases.

Keywords: COVID-19; fibrosis; infection; inflammation; macrophage.

Figure 1

Macrophage subsets in the steady state and in defense. There are two populations of macrophages in the physiological state and three populations of macrophages in the injury and inflammatory states. In the steady-state condition, the maturation and self-maintenance of TR-AMs rely on GM-CSF and TGF-β. When injury occurs, monocytes recruit to the alveolar lumen and develop into macrophages, constituting a second group of alveolar macrophages and causing tissue damage by releasing cytokines. TR-AMs can indirectly affect the functions of Mo-AMs and other myeloid cells by inducing epithelial cells to release GM-CSF (12). Whether there is a direct interaction between TR-AMs and Mo-AMs is still unclear.

Figure 2

The role of Macrophages in secondary infection and trained immunity. After a mild infection caused by a specific pathogen such as adenoviruse, TR-AMs upregulate MHC II expression in response to CD8+ T lymphocytes and are rapidly activated in secondary infections (81). Mo-AMs that persists in the alveolar cavity after primary infection are also more likely to be activated and form part of trained AMs. After recovery from severe infections, TR-AMs are paralyzed with reduced phagocytosis and are more susceptible to secondary infections.