Single-cell transcriptome analysis of liver immune microenvironment changes induced by microplastics in mice with
Wangrui Liu1, Meng Li2, Huaqi Guo3
1Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Abstract:
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.
Insights
Microplastics (MPs) worsen non-alcoholic fatty liver disease (NAFLD) by increasing inflammation and altering immune cell populations in mice. This study reveals MPs
Area of Science:
- Environmental Health
- Toxicology
- Immunology
Background:
- Microplastics (MPs) are environmental contaminants that can enter organisms and potentially cause metabolic issues.
- Non-alcoholic fatty liver disease (NAFLD) is a growing health concern, but the role of MPs in its development is not fully understood.
- Investigating the immune microenvironment's response to MP exposure in NAFLD is crucial.
Purpose of the Study:
- To investigate the impact of microplastic exposure on the immune microenvironment in a mouse model of non-alcoholic fatty liver disease (NAFLD).
- To elucidate the cellular and molecular mechanisms by which MPs exacerbate NAFLD progression.
- To identify specific immune cell population changes associated with MP exposure in NAFLD.
Main Methods:
- Mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD) with or without microplastic (MP) administration.
- Unbiased single-cell RNA-sequencing (scRNA-seq) was employed to analyze the liver's cellular pathology and immune cell landscape.
- Histopathological scoring and transcriptomic atlas construction were performed to assess NAFLD activity and cellular changes.
Main Results:
- High-fat diet (HFD) significantly increased NAFLD activity scores; MP administration further worsened liver steatosis, inflammation, and ballooning degeneration.
- Single-cell RNA-sequencing revealed MP exacerbation of pro-inflammatory responses and altered hepatocyte stemness during HFD feeding.
- MPs increased liver-infiltrating Vsig4+ macrophages while decreasing S100A6+ macrophages, alongside increased CD4+ T cell recruitment and CD8+ T cell exhaustion.
Conclusions:
- Microplastic exposure exacerbates NAFLD progression by worsening liver pathology and dysregulating the immune microenvironment.
- MPs significantly alter macrophage populations and T cell responses, contributing to immune dyshomeostasis and inflammation in NAFLD.
- This study provides critical insights into the cellular mechanisms underlying MP-induced NAFLD development.
