Human Monocyte-Derived\nMacrophages Demonstrate Distinct\nResponses to Ambient Particulate Matter in a Polarization State- and\nParticle Seasonality-Specific Manner

Macrophages are professional phagocytic immune cells\nthat, following\nactivation, polarize on a spectrum between the proinflammatory M1\nand the proresolution M2 states. Macrophages have further been demonstrated\nto retain plasticity, allowing for the reprogramming of their polarization\nstates following exposure to new stimuli. Particulate matter (PM)\nhas been repeatedly shown to modify macrophage function and polarization\nwhile also inducing worsening respiratory infection morbidity and\nmortality. However, limited work has considered the impact of the\ninitial macrophage polarization state on subsequent responses to PM\nexposure. PM composition can demonstrate seasonality-specific compositional\nchanges based on differences in seasonal weather patterns and energy\nneeds, introducing the need to consider the seasonality-specific effects\nof airborne PM when investigating its impact on human health. This\nstudy sought to determine the impact of airborne PM collected during\ndifferent seasons of the year in Xinxiang, China, on macrophage function\nin a polarization state-dependent manner. Macrophages were differentiated\nusing the macrophage colony-stimulating factor (M-CSF) on CD14+CD16–\nmonocytes isolated from the blood of healthy human volunteers. The\nresulting macrophages were polarized into indicated states using well-characterized\npolarization methods and assessed for phagocytic function, bioenergetic\nproperties, and secretory profile following exposure to PM collected\nduring a single day during each season of the year. Macrophages demonstrated\nclear polarization state-dependent phagocytic, bioenergetic, and secretory\nproperties at the baseline and following PM exposure. Specific PM\nseasonality had a minimal impact on phagocytic function and a minor\neffect on bioenergetic properties but had clear impacts on the secretory\nprofile as demonstrated by the enriched secretion of well-characterized\nmediator clusters by particle season. Together, these data suggest\nthat both particle seasonality and macrophage polarization state must\nbe considered when investigating the impact of PM on macrophage function.\nThese factors may contribute to the negative outcomes linked to PM\nexposure during respiratory infections.