Single-Cell Insights Into Macrophage Subtypes in Pulmonary Infections

Macrophages are pivotal innate immune cells that play essential roles in pathogen recognition, inflammation modulation, and tissue repair during pulmonary infections. Macrophages have remarkable plasticity that is shaped by diverse external stimuli to adapt to the dynamic lung microenvironment. Traditional models of macrophage polarization (M1/M2) cannot capture the full complexity of macrophage heterogeneity and diverse functions during lung infections. Recent advances in single-cell omics have provided new insights into distinct macrophage subtypes, revealing their unique transcriptional profiles across various stages of infection. This review focuses on the functional plasticity of pulmonary macrophages and how environmental cues modulate their activation and effector functions. An integrative classification framework that defines six major functional macrophage subtypes in pulmonary infections, based on single-cell omics with functional perspectives is proposed. This framework refines the understanding of macrophage heterogeneity and offers a foundation for developing targeted immunotherapeutic strategies against lung infections.