Chronic Early-Life Exposure to Dicyclohexyl Phthalate (DCHP) Impairs Host Defense in Caenorhabditis elegans and Is Associated with Transcriptional Alterations in p38 MAPK and Insulin-like Signaling Pathways
TL;DR
It is suggested that DCHP may impair innate immune function through transcriptional alterations in immune- and stress-response pathways, although direct pathway activation or inhibition was not demonstrated.
Abstract
Dicyclohexyl phthalate (DCHP) is a widely used plasticizer, but its potential impact on immunity remains largely unexplored. In this study, synchronized L1-stage Caenorhabditis elegans were exposed to 0.0001–0.1 g/L DCHP for 72 h to investigate the effects of chronic early-life exposure on innate immunity; 0.01 and 0.1 g/L were used for subsequent mechanistic analyses. Innate immune function was evaluated using Pseudomonas aeruginosa PA14 survival assays, RT-qPCR, mutant strains, and oxidative-stress-related measurements. Chronic exposure beginning at the L1 stage significantly reduced the survival of C. elegans infected with Pseudomonas aeruginosa PA14. This immunosuppression was associated with increased daf-2 and age-1 transcript levels and reduced daf-16 transcript levels, indicating transcriptional alterations in insulin-like signaling-related genes. Additionally, the expression of pmk-1, nsy-1, and sek-1, key components of the p38 MAPK pathway, was markedly downregulated. Survival assays using different mutants supported the involvement of insulin-like signaling- and p38 MAPK-related genes in the decline in innate immunity following DCHP exposure. Furthermore, DCHP exposure reduced the expression of stress resistance genes, including skn-1, and several antioxidant enzymes. These findings suggest that DCHP may impair innate immune function through transcriptional alterations in immune- and stress-response pathways, although direct pathway activation or inhibition was not demonstrated.