Beauvericin modulates immune responses in the silkworm, Bombyx mori: insights from cellular and transcriptomic analyses.

Despite the well-documented cytotoxic effects of beauvericin (BEA), its specific interactions with the insect immune system remain inadequately explored. This study systematically investigated the impact of BEA on the immune response of the silkworm, Bombyx mori. Larvae were exposed to BEA (0.5-10 μM) to determine the LC50 and evaluate key immune responses: hemocyte counts, viability, phagocytosis, nodulation, encapsulation, and PO activity, alongside transcriptomic analysis by RNA-Seq. BEA exhibited an LC50 of 5.23 μM in silkworm larvae. While it suppressed hemocyte viability, it paradoxically induced a hyperactive immune state. This was characterized by a dynamic, biphasic response in total hemocyte count, a significant increase in granulocytes, and the potentiation of key immune functions-including phagocytosis, nodulation (with nodules up to 119 μm × 41 μm), encapsulation, and phenoloxidase (PO) activity, all of which peaked at 12 h. Transcriptomic analysis revealed 722 differentially expressed genes, implicating disruptions in the Toll, Imd, and MAPK signaling pathways, alongside detoxification pathways. We conclude that BEA-triggered immune hyperactivity, particularly the excessive melanization response, ultimately contributes to larval mortality. These findings provided a theoretical foundation for understanding BEA's immunotoxicity and introduced a novel mechanism of pathogenicity via immune hyperactivation, thereby expanding our knowledge of fungal toxin biology and insect immunology.