Immersion-Based Candida albicans Infection in Adult Zebrafish Induces Distinct Behavioral, Immune and Oxidative Responses in a Dose- and Time-Dependent Manner

Candidiasis caused by Candida albicans represents a major opportunistic infection, particularly in hospitalized individuals, with high morbidity and mortality rates. Experimental models that reproduce natural routes of exposure and allow integrated analyses of host responses remain limited. In this study, we established and characterized an immersion-based infection model of C. albicans in adult zebrafish (Danio rerio) to investigate systemic, behavioral, immunological, oxidative, and histopathological outcomes. Adult zebrafish were exposed by immersion to different fungal concentrations (1 × 10⁶ or 1 × 10⁸ CFU/mL) for 10-24 h. Fungal burden, exploratory behavior, antioxidant capacity (ABTS), TNF-α levels, and tissue alterations were subsequently assessed. Exposure to 1 × 10⁸ CFU/mL for 24 h resulted in a significant increase in fungal burden without inducing mortality, characterizing a sublethal infection. Infection modulated behavioral parameters, tissue-specific alterations in antioxidant activity and a marked reduction of TNF-α levels in the liver and brain were observed, suggesting disruption of immune-redox homeostasis. Histopathological analyses revealed mild inflammatory responses and increased melanomacrophage accumulation, particularly in skin and gills tissues. Overall, this study demonstrates that adult zebrafish immersion constitutes a biologically relevant and translational model for investigating candidiasis, enabling integrated evaluation of host-pathogen interactions and systemic responses under environmentally relevant conditions.