2. Academic Validation
  3. Polystyrene microplastic-induced pathophysiology is driven by disruption of efferocytosis

Polystyrene microplastic-induced pathophysiology is driven by disruption of efferocytosis

  • Immunity. 2026 Mar 10;59(3):618-636.e11. doi: 10.1016/j.immuni.2026.01.009.
Ana C Codo 1,  Jesus E Romero-Pichardo 2,  Zhaoquan Wang 1,  Mariano A Aufiero 3,  Tomi Lazarov 4,  Waleska Saitz Rojas 4,  Nicole S Walker 5,  Achuth Nair 2,  Roger F Cole 6,  Savannah Adkins 4,  Edward Dong 4,  Kelvin Fadojutimi 7,  Celia Martínez de la Torre 8,  Yael David 9,  Tobias M Hohl 10,  Frederic Geissmann 11,  Kayvan R Keshari 12,  Christopher D Lucas 13,  Justin S A Perry 14
Affiliations

Affiliations

  • 1 Immunology & Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 2 Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 3 Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 4 Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 5 Tri-Institutional Program in Chemical Biology, New York, NY, USA; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 6 Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; ACCESS Summer Research Program, Weill Cornell Medicine, New York, NY, USA; University of Central Florida, Orlando, FL, USA.
  • 7 Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Bridge Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 8 Department of Radiology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 9 Tri-Institutional Program in Chemical Biology, New York, NY, USA; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA; Department of Physiology, Biophysics, and System Biology, Weill Cornell Medicine, New York, NY, USA.
  • 10 Immunology & Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immuno-Oncology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Infectious Disease Service, Department of Medicine, Memorial Hospital, New York, NY, USA.
  • 11 Immunology & Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 12 Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Bridge Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Radiology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.
  • 13 University of Edinburgh Centre for Inflammation Research, Edinburgh BioQuarter, UK; Institute for Regeneration and Repair, Edinburgh BioQuarter, UK.
  • 14 Immunology & Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: [email protected].
PMID: 41742421 DOI: 10.1016/j.immuni.2026.01.009
Abstract

Microplastics (MPs), microparticles from plastic degradation, pose a substantial threat to human health. Macrophages, the body's immune sentinels, are unable to break down MPs, suggesting that MP accumulation could impair essential functions, such as removal of apoptotic cells (ACs), termed efferocytosis. We found that polystyrene MP (PS-MP) accumulation disrupted efferocytosis by impairing AC digestion in multiple types of macrophages and Sertoli cells, specialized testes phagocytes, in vitro. PS-MP exposure also suppressed efferocytosis and caused damage in the lungs, liver, and testes in vivo. Mechanistically, PS-MP-loaded efferocytotic macrophages had dysregulated metabolic and phagolysosome processes, including accumulation of methylglyoxal (MGO) and increased MGO glycation of glucose-6-phosphate dehydrogenase, an enzyme required for AC digestion. Consistently, we found that overexpression of the MGO detoxification glyoxalase-1 rescued PS-MP-induced defects in AC digestion in vitro and in vivo. Collectively, we demonstrate that PS-MPs directly disrupt efferocytosis, which negatively affects the function and health of multiple organs.

Keywords

efferocytosis; immunometabolism; methylglyoxal; microplastics; phagocytosis; polystyrene; tissue-resident macrophages.

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