Candida albicans-Based Immune Training to Reduce Lung Fibrosis from Polystyrene Nanoparticles.

Polystyrene nanoparticles (PS-NPs) present significant risks to respiratory health, contributing to lung fibrosis. Current therapeutic strategies for PS-NP exposure injuries are limited and often ineffective. One promising solution is immunological training. This study explores the novel role of Candida albicans in immune training to alleviate PS-NP-induced fibrosis. Our findings demonstrate that C. albicans enhances immune responses in a unique way, advancing current frameworks of trained immunity and offering new therapeutic approaches for health issues related to environmental pollutants. We conducted experiments using male BALB/c mice exposed to 80 nm PS-NPs via posterior pharyngeal drip. Prior to exposure, the mice received an intravenous injection of low-dose C. albicans to induce immunological training. To evaluate the protective effects of C. albicans, we assessed survival rates, pulmonary histopathology, and gene expression profiles. The results indicated that while 100% of the control group exposed to PS-NPs did not survive, the group pre-treated with C. albicans exhibited complete survival. Histopathological analysis revealed preserved lung architecture and a significant reduction in collagen deposition in the C. albicans + PS-NPs group compared to the PS-NPs only group. Additionally, RNA sequencing analysis identified a total of 415 differentially expressed genes, including five upregulated circadian rhythm genes (Per3: 1.93-fold, Rorc: 1.69-fold, Cry1: 2.01-fold, Per1: 2.55-fold, Per2: 2.73-fold) and one downregulated circadian rhythm gene (Npas2: 0.42-fold) in the C. albicans + PS-NPs group compared to the PS-NPs group. C. albicans-based immune training reduces lung fibrosis and enhances survival after PS-NP exposure, suggesting a promising therapeutic strategy.