Size-dependent plastic exposure disrupts macrophage function and tissue-specific metabolism

Makdissi N, Viola MF, Steinheuer LM, Blank-Stein N, Kardinal R, Musacchio F, Franco Taveras E, Aliprandi V, Sieckmann K, Abdulkadyrov A, Mayer ML, Diefenbach-Wilke ML, Fink D, Beckert H, Böhmdorfer S, Deveuve Q, Graelmann FJ, Mauel K, Kronau N, Thomas J, Bejarano D, Schlitzer A, Högler S, Yaghmour MH, Heeren J, Thiele C, Kenner L, Meissner F, Nimmerjahn F, Fuhrmann M, Wachten D, Thurley K, Mass E (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Nature Metabolism Nature Research

DOI: 10.1038/s42255-026-01615-8

Abstract

Plastic pollution is an emerging yet understudied environmental risk to the immune system. Once ingested, microplastic and nanoplastic particles (MNPs) can translocate from the gut to internal organs1, 2–3, with macrophages serving as primary targets4. Kupffer cells (KCs), the liver-resident macrophages, have a central role in immune surveillance and metabolism5, yet their response to MNPs remains unclear. Here we identify KCs as the primary hepatic reservoir for MNPs in young male mice. Chronic plastic exposure over 12 weeks alters their transcriptional profile, impairs phagocytic function and is associated with metabolic dysregulation of hepatocytes. Microplastics, but not nanoplastics, reduce KC-mediated clearance of circulating cells. Under diet-induced obesity, microplastics exacerbate hepatic lipid accumulation, while nanoplastics alter systemic glucose metabolism and energy expenditure. These findings demonstrate that chronic MNP exposure disrupts macrophage function in a size-dependent manner, with subsequent distinct consequences for liver and systemic metabolism.

Authors with CRIS profile

Nikola Makdissi
Quentin Deveuve Lehrstuhl für Genetik Falk Nimmerjahn Lehrstuhl für Genetik

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Universität für Bodenkultur Wien (BOKU) / University of Natural Resources and Life Sciences, Vienna AT Austria (AT) Medizinische Universität Wien AT Austria (AT) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE)

How to cite

APA:

Makdissi, N., Viola, M.F., Steinheuer, L.M., Blank-Stein, N., Kardinal, R., Musacchio, F.,... Mass, E. (2026). Size-dependent plastic exposure disrupts macrophage function and tissue-specific metabolism. Nature Metabolism. https://doi.org/10.1038/s42255-026-01615-8

MLA:

Makdissi, Nikola, et al. "Size-dependent plastic exposure disrupts macrophage function and tissue-specific metabolism." Nature Metabolism (2026).

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