Differential immunotoxicity effects of triclosan and triclocarban on larval zebrafish based on RNA-Seq and bioinformatics analysis

Abstract

Herein, we demonstrated that sublethal-dose exposure to triclosan (TCS) and triclocarban (TCC) triggered larval zebrafish immunotoxicity. Acute exposure to TCS induced significant increases in larval neutrophils and macrophages and a prominent decrease in thymic T cells. In contrast, three kinds of cells (neutrophils, macrophages, and thymic T cells) were significantly reduced under TCC exposure, suggesting that both TCS and TCC suppress thymus development and mature T-cell differentiation. TCC was confirmed to have more severe immunotoxicity than TCS. Using Illumina RNA-Seq, 581 and 738 differentially expressed genes (DEGs) were identified in the TCS and TCC treatments, respectively. GO function and KEGG pathway enrichment analyses revealed that the DEGs were not identical in terms of biological processes, cellular components and molecular functions, but were primarily involved in immune response. KEGG analysis showed that approximately 47% and 11% of DEGs were mainly enriched in the immune system of the TCC and TCS treatments, respectively. Protein-protein interaction (PPI) network analysis confirmed that the hub genes enriched in the immune-related pathways differed between TCS and TCC exposure. The hub genes were fynb, mapk12b, scarb1, pik3r2, prkg3, srfa, arhgef2, cldn15la, and cldn15lb in the TCS treatment, and plg, serping1, masp2, fgg, vtnb, mmp9, serpine1, il1b, sb:cb37 and stat3 in the TCC treatment. Molecular docking simulation demonstrated that both TCS and TCC were stably docked with their target hub genes, and that their target molecules for inducing immunotoxicity were different. The differential target molecules and action pathways induced by TCS and TCC exposure provide us with diagnostic targets and toxicological endpoints.