Microplastics inhibit macrophage bioenergetics impairing homeostatic function and immune responsiveness

Abstract Since the 1950s, microplastics (MPs) have become omnipresent, representing a novel environmental hazard which continually deposits in our airways. Pulmonary macrophages (pMacs) orchestrate the balance between inflammation and tolerance required for homeostasis of the lung and are among the first immune cells to encounter inhaled MPs. Yet, how pMacs react to plastic deposition in the lung and implications for disease remain unknown. Here, we exposed mice in vivo, human precision-cut lung slices (hPCLS) ex vivo, and monocyte-derived macrophages and cell lines to polystyrene MPs in vitro. MP deposition in the lung and extrapulmonary tissues was determined over a 1-week period and pMacs from MP-laden lungs isolated for RNA-sequencing. We compared the effects of MPs or diesel exhaust particulate exposures on hPCLS viability and metabolism, monocyte-derived macrophage transcription, and macrophage mitochondrial function, inflammation, and antigen presentation. MPs readily translocated the lung and were observed in all organs examined within 1-day. pMacs from MP-exposed mice expressed transcriptional pathways associated with endocrine system disorders, tissue remodeling, and malignant disease. Macrophage phagocytosis was impaired through decreased mitochondrial function which could be rescued pharmacologically. MPs inhibited the ability of macrophages to effectively present OVA-antigen preventing TCR-specific activation, an effect that could be restored by blocking PD-1/PD-L1. These findings indicate that MPs impair macrophages via unique mechanisms linking phagocytic and bioenergetic dysfunction. Loss of antigen-presenting capabilities in MP-laden macrophages may compromise immunosurveillance. As such, MPs have the potential to increase susceptibility to lung disease independent of the conventional mechanisms of inflammation and oxidative stress.