Abstract
Anti-inflammatory and proinflammatory responses in macrophages are influenced by cellular metabolism. Macrophages are the primary phagocyte in mucosal environments (i.e., intestinal tract and lungs) acting as first-line defense against microorganisms and environmental pollutants. Given the extensive contamination of our food and water sources with microplastics, we aimed to examine the metabolic response in macrophages to microplastic particles (MPs). Utilizing murine macrophages, we assessed the metabolic response of macrophages after polystyrene MP phagocytosis. The phagocytosis of MP by macrophages induced a metabolic shift toward glycolysis and a reduction in mitochondrial respiration that was associated with an increase of cell surface markers CD80 and CD86 and cytokine gene expression associated with glycolysis. The gastrointestinal consequences of this metabolic switch in the context of an immune response remain uncertain, but the global rise of plastic pollution and MP ingestion potentially poses an unappreciated health risk.
Graphical abstract

Macrophage phagocytosis of microplastics alters cellular metabolism.
- Macrophages cannot degrade PS MP.
- MP phagocytosis increases glycolysis in murine macrophages.
- MP phagocytosis reduces mitochondrial respiration in murine macrophages.
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‘Not applicable’.
Abbreviations
- ECAR:
-
Extracellular acidification rate
- GRA:
-
Glycolytic rate assay
- IBD:
-
Inflammatory bowel disease
- IEC:
-
Intestinal epithelial cell
- LAP:
-
LC3-associated phagocytosis
- MFI:
-
Mean fluorescence intensity
- mitoOCR:
-
Mitochondrial oxygen consumption rate
- MP:
-
Microplastic particles
- PER:
-
Proton efflux rate
- TCA:
-
Tricarboxylic acid cycle
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Funding
This work was supported in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) through grant no. UL1TR001449 (EFC), in part by NIH grant 1R56ES032037-01 (E.F.C.), in part by NIH grant P20GM121176 (EFC), P20GM130422 (MJC), and New Mexico Medical Trust C-2446-RAC (EFC). SMG was supported in part by the Infectious Disease and Inflammation Program Pre-doctoral T32 training grant, NIH/NIAID grant T32AI007538.
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SDM participated in writing the manuscript and performed all experiments with help from HCM, JMH, CLL, and JW. SMG performed confocal microscopy. MJC provided critical reagents and helped design the study. EFC designed the study, analyzed data, and wrote the paper. All authors approved the final version of the manuscript.
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All experiments were approved by the Institutional Animal Care and Use Committee of the University of New Mexico Health Sciences Center, in accordance with the National Institutes of Health guidelines for use of live animals. The University of New Mexico Health Sciences Center is accredited by the American Association for Accreditation of Laboratory Animal Care.
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Merkley, S.D., Moss, H.C., Goodfellow, S.M. et al. Polystyrene microplastics induce an immunometabolic active state in macrophages. Cell Biol Toxicol 38, 31–41 (2022). https://doi.org/10.1007/s10565-021-09616-x
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DOI: https://doi.org/10.1007/s10565-021-09616-x