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

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Nikola Makdissi , Maria Francesca Viola , Lisa M Steinheuer , Nelli Blank‐Stein , Eliana Franco Taveras , Fabrizio Musacchio , Katharina Sieckmann , Ronja Kardinal , Quentin Deveuve , Frederike Graelmann , Katharina Mauel , Nele Kronau , Jake Thomas , David Alejandro Bejarano , Sandra Hoegler , Mohammed Yaghmour , Joachim L. Schultze , Christoph Thiele , Lukas Kenner , Andreas Schlitzer , Falk Nimmerjahn , Dagmar Wachten , Martin Fuhrmann , Kevin Thurley , Elvira Mass ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.21203/rs.3.rs-6204281/v1

Plastic pollution is an emerging yet understudied environmental risk to the immune system. Once ingested, nano- and microplastic particles (MNPs) can translocate from the gut to internal organs, with macrophages serving as primary targets. Kupffer cells (KCs), the liver-resident macrophages, play a central role in immune surveillance and metabolism, yet their response to MNPs remains unclear. Here, using a chronic plastic exposure model in mice, we identify KCs as the primary hepatic reservoir for MNPs. Long-term exposure alters their transcriptional profile and impairs phagocytic function, leading to metabolic dysregulation of hepatocytes. Microplastics, but not nanoplastics, reduce KC-mediated clearance of circulating cells and bacteria. Under diet-induced obesity, microplastics exacerbates hepatic lipid accumulation, while nanoplastics impair systemic glucose metabolism. Although the blood-brain barrier limits microplastic infiltration, a small fraction of ingested nanoplastics reaches the brain, where it is taken up by microglia, the brain-resident macrophages. However, we observe no signs of neuroinflammation or behavioral deficits. These findings demonstrate that chronic MNP exposure disrupts macrophage function in a size-dependent manner, with distinct consequences for liver and systemic metabolism, while the brain remains largely protected. Understanding tissue-specific vulnerabilities to MNPs is crucial for assessing their long-term health impact.

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Function (biology) Macrophage Metabolism Cell biology Biology Biochemistry In vitro

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Type: preprint
Language: en
Landing Page: https://doi.org/10.21203/rs.3.rs-6204281/v1
PDF: https://www.researchsquare.com/article/rs-6204281/latest.pdf
OA Status: gold
Related Works: 10
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DOI: https://doi.org/10.21203/rs.3.rs-6204281/v1

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

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Type: preprint

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Language: en

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Publication year: 2025

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Publication date: 2025-03-18

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Authors: Nikola Makdissi, Maria Francesca Viola, Lisa M Steinheuer, Nelli Blank‐Stein, Eliana Franco Taveras, Fabrizio Musacchio, Katharina Sieckmann, Ronja Kardinal, Quentin Deveuve, Frederike Graelmann, Katharina Mauel, Nele Kronau, Jake Thomas, David Alejandro Bejarano, Sandra Hoegler, Mohammed Yaghmour, Joachim L. Schultze, Christoph Thiele, Lukas Kenner, Andreas Schlitzer, Falk Nimmerjahn, Dagmar Wachten, Martin Fuhrmann, Kevin Thurley, Elvira Mass

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Landing page: https://doi.org/10.21203/rs.3.rs-6204281/v1

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PDF URL: https://www.researchsquare.com/article/rs-6204281/latest.pdf

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Concepts: Function (biology), Macrophage, Metabolism, Cell biology, Biology, Biochemistry, In vitro

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