Xenium-based spatial transcriptomics of brains following chronic plastic exposure. 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. Overall design: 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.

塑料污染对免疫系统构成了一种普遍却尚未得到充分研究的环境风险。一旦被摄入，纳米塑料与微塑料颗粒（MNPs）可通过循环系统从肠道转移至内脏器官。在人体中，研究人员已在颈动脉斑块内的巨噬细胞中检测到MNPs，这表明这些具有强吞噬活性的细胞在稳态条件下也可能是MNPs的关键作用靶点。库普弗细胞（KCs）是定居于肝脏的巨噬细胞，它们通过调节代谢、清除调理化靶细胞以及作为抵御细菌的第一道防线，在肝脏稳态维持中发挥关键作用。定居于肝血窦内的库普弗细胞会持续监测血液循环，高效捕获并清除病原体与循环颗粒，以此维持免疫与代谢平衡⁵。目前尚不明确库普弗细胞是否能有效捕获并储存MNPs，以及这一过程会如何影响肝脏功能。本研究利用慢性塑料暴露小鼠模型，探究摄入的MNPs如何影响库普弗细胞的核心功能，进而对肝脏功能产生影响。研究结果表明，库普弗细胞是MNPs在肝脏中的主要作用靶点；12周的塑料暴露会改变其转录组，并削弱吞噬能力，进而导致肝脏代谢紊乱。仅微塑料（而非纳米塑料）暴露会降低库普弗细胞介导的循环细胞与细菌清除能力，并加剧饮食诱导的肥胖。上述研究结果表明，慢性MNPs暴露会以颗粒尺寸依赖的方式破坏组织特异性巨噬细胞功能，对肝脏功能与整体健康产生显著的长期影响。实验整体设计：选取8~10周龄的雄性C57Bl6/J小鼠，每周通过口饲法分别给予磷酸盐缓冲液（PBS）、100mg/kg的50nm聚苯乙烯颗粒或500nm聚苯乙烯颗粒。暴露12周后，对小鼠实施安乐死并进行经心脏灌流，取出脑组织后立即进行包埋，并置于液氮中快速冷冻。