Parental polystyrene nanoplastics exposure increases susceptibility to pathogen infection in offspring via H3K36me3-UPR

Plastic pollution, particularly nanoplastics, poses a serious threat to the health of humans and wildlife. Using Caenorhabditis elegans as a model, we found that exposure to polystyrene nanoplastics (PS-NPs) at 1000 μg/L for 48 h significantly reduced survival upon Pseudomonas aeruginosa PA14 infection in the parental generation (P0), with a 42.74% decline. Notably, this impaired immunity was also observed in the first filial generation (F1) and second filial generation (F2), where survival decreased by 31.27% and 19.55%, respectively. This transgenerational decline in innate immunity was not attributable to residual nanoplastics in the progeny but was mediated through H3K36me3-dependent epigenetic regulation. Mechanistically, PS-NPs suppressed the endoplasmic reticulum unfolded protein response (UPRER), particularly the IRE-1/XBP-1 pathway, and downregulated collagen-related genes, thereby compromising epithelial defenses. ChIP-qPCR and Western blotting further confirmed reduced H3K36me3 enrichment on UPRER and collagen gene promoters. Importantly, this epigenetic inheritance occurred independently of small RNAs or N6-mA DNA methylation. Collectively, these findings reveal an unrecognized mechanism by which nanoplastic exposure weakens immunity across generations through histone modification, underscoring the long-term biological risks posed by environmental nanoplastics.