Differentiating micro- and nanoplastics immunotoxicity to oyster gills at single-cell resolution level

Oyster gills function as a filter-feeding organ and the first line of immune defense, constituting a primary site for microplastic interaction and toxicity. However, tissue heterogeneity of oyster gills obscures the immunotoxicity induced by micro- and nanoplastics (MPs/NPs). Here, we reported the toxicity of MPs and NPs on bivalve gills at the single-cell level. This study indicated that at comparable particle concentration (200 μg/L), NPs displayed higher accumulation potential than MPs, with distinct histopathology induced by MPs and NPs. scRNA-seq analysis revealed that NPs specifically targeted prohemocytes (PHCs), reducing their population by 47.0% and disrupting their differentiation trajectory. In contrast, MPs significantly reduced epithelial cell numbers and disrupted the temporal dynamics of subtype differentiation. NPs dysregulated the SEMA6-PLXNA neuroimmune pathway, altering the role of PHCs from signal senders to receivers, which subsequently activated the autophagy and inhibited the CD45 immune checkpoint. MPs triggered compensatory proliferation of macrophage-like cells (MLCs) via the CADM pathway. Pseudotime analysis further revealed that NPs disrupted the dynamic expression of ribosomal genes, thereby blocking the differentiation trajectory of PHCs, MLCs, and GCs. This study provides the first immune-cell atlas of bivalve gills and proposes a differentiation-blockade index coupled with a dual biomarker system (neural-cell stability/PHC loss rate) for diagnosing MNPs toxicity. © 2024 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.