Xenium-based spatial transcriptomics of brains following chronic plastic exposure

Plastic pollution poses a universal yet understudied environmental risk to the immune system. Once ingested, nano- and microplastic particles (MNPs) can translocate from the gut into internal organs, likely via circulation. In humans, MNPs have been detected in macrophages within carotid artery plaques, suggesting that these highly phagocytic cells, may also serve as key targets for MNPs under homeostatic conditions. Kupffer cells (KCs), the liver-resident macrophages, play a crucial role in liver homeostasis by regulating metabolism, clearing opsonized target cells, and serving as the first line of defence against bacteria. Residing within the liver sinusoids, they continuously monitor the bloodstream, efficiently capturing and eliminating pathogens and circulating particles to maintain immune and metabolic balance5. It remains unknown whether KCs efficiently capture and store MNPs and how this might affect liver function. Here, we utilize a mouse model of chronic plastic exposure to assess how ingested MNP influence KC core functions, and thereby also liver function. We show that KCs are the primary hepatic target of MNPs and that 12 weeks of exposure alters their transcriptome and impairs phagocytic capacity, leading to dysregulated liver metabolism. Microplastics, but not nanoplastics, exposure reduces KC-mediated clearance of circulating cells and bacteria and exacerbates diet-induced obesity. These findings suggest that chronic MNP exposure disrupts tissue-specific macrophage functions in a size-dependent manner, with distinct long-term consequences for liver function and overall health. 8-10 week old male C57Bl6/J mice received weekly oral gavages of either PBS, 100mg/kg 50nm polysterene particles or 500nm polysterene particles. After 12 weeks, mice were euthanised a perfused trans-cardially, the brain was dissected and immediately embedded and snap-frozen in liquid nitrogen.