Intestinal Toxicity of Metal Nanoparticles: Silver Nanoparticles Disorder the Intestinal Immune Microenvironment

[Image: see text] Albeit numerous studies have been conducted on the toxicity evaluation of engineered metal nanoparticles (NPs), significant knowledge gaps remain regarding the influence of oral exposure to metal NPs on the intestine system, especially the effects on the intestinal immune microenvironment. Herein, we examined the long-term effects of representative engineered metal NPs on the intestine through oral exposure and identified silver NPs (Ag NPs) that resulted in severe damage. Oral Ag NP exposure damaged the epithelial structure, reduced the thickness of the mucosal layer, and altered the intestinal microbiota. Particularly, the reduced thickness of the mucosal layer increased the phagocytosis of Ag NPs by dendritic cells (DCs). Comprehensive animal and in vitro experiments unraveled that Ag NPs directly interacted with DCs, resulting in the abnormal activation of DCs by generating reactive oxygen species and inducing uncontrolled apoptosis. Furthermore, our data unveiled that the interactions between Ag NPs and DCs reduced the proportion of CD103(+)CD11b(+) DCs and induced Th17 cell activation with inhibition of regulatory T-cell differentiation, resulting in the disordered immune microenvironment in the intestine. Collectively, these results represent a new point of view on the cytotoxicity of Ag NPs on the intestine system. This study provides additional insights into the health risks of engineered metal NPs, especially Ag NPs.