Trained immunity induction by β-glucan under distinct immune training schemes in a mouse model

Although trained immunity has been explored in various experimental models, the effects of oral β-glucan administration in mice and in vivo comparisons of different training intervals remain unexplored. First, this study evaluated the ability of β-glucan from Debaryomyces hansenii CBS 8339 (βG-Dh) to induce trained immunity in mice through oral administration at different doses. BALB/c mice received oral βG-Dh (0.5, 1, or 2 mg), oral zymosan (1 mg), or intraperitoneal zymosan (1 mg; positive control), followed by ex vivo stimulation of splenocytes with LPS. Low (0.5 mg) and medium (1 mg) doses of βG-Dh significantly enhanced cell viability, nitric oxide production, and myeloperoxidase activity. βG-Dh also increased glucose consumption and lactate production, indicating glycolytic changes associated with trained immunity. In addition, different training schemes were assessed by varying the time intervals (7, 11, and 15 days) between stimulus and challenge. Only the long-time protocol was associated with higher cell survival, increased myeloperoxidase activity, and metabolic changes consistent with a trained immunity phenotype. Overall, these results highlight the critical role of both dosage and stimulation interval in shaping trained immunity outcomes and provide new insights for optimizing β-glucan-based strategies to modulate innate immune memory.