Chronic exposure to di(2-ethylhexyl) phthalate (DEHP) weakens innate immunity and leads to immunosenescence in C. elegans

Di(2-ethylhexyl) phthalate (DEHP), a widespread contaminant, has numerous adverse impacts on human health and ecosystems. Chronic DEHP exposure has been found to accelerate aging; however, its potential threat to age -dependent innate immune decline remains unknown. This study aims to evaluate the effects of chronic DEHP exposure on innate immunosenescence in Caenorhabditis elegans. We show that the length of the exposure period significantly impacts DEHP-induced age-related declines, which is linked to immunosenescence and oxidative stress. We found that the DEHP-caused immunosenescence is accompanied with downregulation of an antimi-crobial gene lys-7 as well as an enhancement of the nuclear translocation of HLH-30, an orthologue of mammalian transcription factor EB (TFEB). Moreover, DEHP exposure increases the expression of riok-1, a human RIO kinase homolog, which is associated with DEHP-induced HLH-30/TFEB translocation. Our findings suggest that early-life and chronic exposure to DEHP, mostly due to parent compound rather than its metabolite mono(2-ethylhexyl) phthalate (MEHP), may weaken the innate immunity in C. elegans and may enhance sus-ceptibility to infections or promote immunosenescence in aged populations.