Human Monocyte-Derived Macrophages Demonstrate Distinct Responses to Ambient Particulate Matter in a Polarization State- and Particle Seasonality-Specific Manner.

Abstract

Macrophages are professional phagocytic immune cells that, following activation, polarize on a spectrum between the proinflammatory M1 and the proresolution M2 states. Macrophages have further been demonstrated to retain plasticity, allowing for the reprogramming of their polarization states following exposure to new stimuli. Particulate matter (PM) has been repeatedly shown to modify macrophage function and polarization while also inducing worsening respiratory infection morbidity and mortality. However, limited work has considered the impact of the initial macrophage polarization state on subsequent responses to PM exposure. PM composition can demonstrate seasonality-specific compositional changes based on differences in seasonal weather patterns and energy needs, introducing the need to consider the seasonality-specific effects of airborne PM when investigating its impact on human health. This study sought to determine the impact of airborne PM collected during different seasons of the year in Xinxiang, China, on macrophage function in a polarization state-dependent manner. Macrophages were differentiated using the macrophage colony-stimulating factor (M-CSF) on CD14+CD16- monocytes isolated from the blood of healthy human volunteers. The resulting macrophages were polarized into indicated states using well-characterized polarization methods and assessed for phagocytic function, bioenergetic properties, and secretory profile following exposure to PM collected during a single day during each season of the year. Macrophages demonstrated clear polarization state-dependent phagocytic, bioenergetic, and secretory properties at the baseline and following PM exposure. Specific PM seasonality had a minimal impact on phagocytic function and a minor effect on bioenergetic properties but had clear impacts on the secretory profile as demonstrated by the enriched secretion of well-characterized mediator clusters by particle season. Together, these data suggest that both particle seasonality and macrophage polarization state must be considered when investigating the impact of PM on macrophage function. These factors may contribute to the negative outcomes linked to PM exposure during respiratory infections.