Polystyrene microplastics trigger intestinal inflammation through CXCL11-mediated T-cell recruitment.

Polystyrene microplastics (PMs) are pervasive aquatic contaminants, yet the molecular mechanisms driving their ecotoxicity, particularly intestinal inflammation, remain poorly elucidated. Here, we investigated the effects of environmentally relevant PMs concentrations (1.0 μm; 0, 25, and 250 μg/L) in zebrafish (Danio rerio). Multi-organ screening identified the intestine as the primary site of inflammation, where PMs were confirmed to accumulate. Exposure of 4 weeks induced significant histopathological damage (2.2-2.7-fold increase in histological scores) and elevated key pro-inflammatory cytokines, including tumor necrosis factor-α (increased by 251.0 %) and interleukin-2 (increased by 81.7 %) at 250 μg/L. Mechanistic investigation using transcriptomics and qPCR revealed the activation of the interferon-gamma (INFγ)-signal transducer and activator of transcription 1 (STAT1) pathway. This activation resulted in the significant upregulation of downstream chemokine genes, notably cxcl11.1 (>2.2-fold). This signaling cascade subsequently promoted T-cell infiltration into the intestine, as confirmed by immunofluorescence (1.8-1.9-fold increase in cluster of differentiation 3ε (CD3ε) intensity and Western blot (2.2-2.3-fold increase in CD3ε protein). Our findings demonstrate that PMs disrupt intestinal homeostasis by triggering an INFγ-STAT1-CXCL11 signaling axis, which heightens C-X-C motif chemokine ligand 11 (CXCL11) expression to drive T-cell recruitment and amplify the inflammatory cascade. This study provides novel molecular insights into PMs-induced immunotoxicity in fish, elucidating a specific pathway of intestinal disruption and highlighting the ecological risks of microplastic pollution.