Monocytes in pneumonia: Functional plasticity and innate memory (Review)

Abstract

Pneumonia remains one of the most prevalent and deadly respiratory diseases worldwide, imposing substantial clinical and socioeconomic burdens. Monocytes (Mos) and their progeny are key components of the innate immune system and perform highly context-dependent roles. The present review summarizes recent advances in understanding Mo biology in pneumonia and discusses current concepts of their functional plasticity. The review first summarizes the developmental origins, phenotypic heterogeneity and functions of circulating Mo subsets, followed by an overview of their recruitment, activation and differentiation in the steady-state and infected lung. Next, the dual, and at times opposing, roles of Mos and their progeny in pneumonia are examined, including contributions to pathogen clearance and microbial immune evasion, the initiation and resolution of inflammation, and tissue repair vs. fibrotic remodeling. Finally, the review highlights emerging evidence showing that pneumonia can induce durable innate immune memory in Mos, their progenitors and the alveolar macrophage compartment. This reprogramming may reshape subsequent pulmonary and systemic immune responses, with important implications for susceptibility to reinfection, chronic lung dysfunction and host resilience. A deeper understanding of Mo plasticity and innate memory may open new avenues for biomarker discovery and host-directed therapeutic strategies for pneumonia.