Propofol decreases the resistance of neutrophils to Candida albicans by inhibiting ferroptosis and the cGAS-STING pathway.

Candida albicans (C. albicans) is a significant fungal pathogen responsible for serious infections, especially in immunocompromised persons. Neutrophils are crucial for innate protection against fungal infections. The anesthetic propofol influences immunological activities, however its impact on neutrophil antifungal activity remains ambiguous. This study examined the effects of propofol on neutrophil responses in humans and mice to C. albicans and evaluated clinical consequences. In vitro, human neutrophils pretreated with propofol exhibited decreased fungal eradication. Propofol diminished glutathione levels, elevated malondialdehyde and ferrous iron concentrations, and inhibited the activation of the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway as well as ferroptosis indicators. In C. albicans-infected mice, propofol diminished renal inflammation, although augmented fungal load and decreased pro-inflammatory cytokines. An analysis of 836 ICU patients with fungal infections from the MIMIC-IV database indicated that propofol-treated patients experienced prolonged hospital stays compared to untreated controls, with no change in fatality rates. Propofol hinders neutrophil clearance of C. albicans by obstructing cGAS-STING signaling and ferroptosis.