Plasma Gelsolin Prevents Organ-Specific Inflammation and Enhances Innate Immune Function in a Systemic Candida albicans Infection

Abstract

Systemic Candida albicans infections (candidemia) remain a significant cause of morbidity and mortality in immunocompromised patients, mainly due to severe inflammation, organ damage, and delayed fungal clearance. Plasma gelsolin (pGSN), an actin-binding protein with immunomodulatory properties, has demonstrated protective effects in bacterial sepsis models, but its role in fungal infections remains unexplored. Here, we evaluated the impact of pGSN in a murine model of candidemia. Mice intravenously challenged with C. albicans exhibited strong inflammatory responses, particularly in the kidneys and lungs, as visualized by IRDye 800CW 2-deoxyglucose imaging and confirmed by histopathological examination. Subcutaneous injection of pGSN significantly reduced systemic and organ-specific inflammation, decreased blood fungal burden, and prevented microabscess formation in the kidneys. In parallel, pGSN suppressed inflammatory gene expression in whole blood and enhanced phagocytic activity of human monocytes. Additionally, pGSN modulated monocyte reactive radical production by increasing nitric oxide and reducing hydrogen sulfide and reactive oxygen species production. These results highlight the dual immunomodulatory and host-protective properties of pGSN, supporting its potential as an adjunctive therapy in fungal sepsis.