Single-cell transcriptome analysis of liver immune microenvironment changes induced by microplastics in mice with non-alcoholic fatty liver

• Published in: The Science of the total environment Vol. 912; p. 168308
• Main Authors: Liu, Wangrui, Li, Meng, Guo, Huaqi, Wei, Shiyin, Xu, Wenhao, Yan, Yuanliang, Shi, Yaoping, Xu, Zhijie, Chang, Kun, Wei, Gang, Zhao, Shuai
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.02.2024
• Subjects: Microenvironment; Microplastics (MPs); Monocyte/macrophage; Non-alcoholic fatty liver disease (NAFLD); scRNA-seq; Monocyte/macrophage; scRNA-seq; Microenvironment; Microplastics (MPs); Non-alcoholic fatty liver disease (NAFLD)
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2023.168308

Recent studies have discovered that tiny particles of microplastics (MPs) at the nano-scale level can enter the body of organisms from the environment, potentially causing metabolic ailments. However, further investigation is required to understand the alterations in the immune microenvironment associated with non-alcoholic fatty liver disease (NAFLD) occurrence following exposure to MPs. Experiments were performed using mice, which were given a normal chow or high-fat diet (NCD or HFD, respectively) plus free drinking of sterile water with or without MPs, respectively. Employing an impartial technique known as unbiased single-cell RNA-sequencing (scRNA-seq), the cellular (single-cell) pathology landscape of NAFLD and related changes in the identified immune cell populations induced following MPs plus HFD treatment were assessed. The results showed that mice in the HFD groups had remarkably greater NAFLD activity scores than those from the NCD groups. Moreover, administration of MPs plus HFD further worsened the histopathological changes in the mice's liver, leading to hepatic steatosis, inflammatory cell infiltrations and ballooning degeneration. Following the construction of a sing-cell resolution transcriptomic atlas of 43,480 cells in the mice's livers of the indicated groups, clear cellular heterogeneity and potential cell-to-cell cross-talk could be observed. Specifically, we observed that MPs exacerbated the pro-inflammatory response and influenced the stemness of hepatocytes during HFD feeding. Importantly, treatment with MPs significantly increase the infiltration of the infiltrating liver-protecting Vsig4+ macrophages in the liver of the NAFLD mouse model while remarkably decreasing the angiogenic S100A6+ macrophage subpopulation. Furthermore, mice treated with MPs plus HFD exhibited significantly increased recruitment of CD4+ cells and heightened exhaustion of CD8+ T cells than those from the control group, characteristics typically associated with the dysregulation of immune homeostasis and severe inflammatory damage. Overall, this study offers valuable perspectives into comprehending the potential underlying cellular mechanisms and regulatory aspects of the microenvironment regarding MPs in the development of NAFLD. [Display omitted] •Liver vulnerability to microplastics heightened with high-fat diets, raising non-alcoholic fatty liver disease risks.•Single-cell transcriptomics shows distinct hepatic changes under normal, microplastic, high-fat, and combined conditions.•Microplastics trigger macrophage and T cell activation, including CD8+ exhaustion, disrupting liver function.•Microplastics with high-fat diets may worsen non-alcoholic fatty liver disease, a new health concern.•Pioneering single-cell RNA sequencing reveals hepatic microplastic toxicity and altered immune cell patterns.