BmMD‐2A responds to 20‐hydroxyecdysone and regulates Bombyx mori silkworm innate immunity in larva‐to‐pupa metamorphosis

Abstract 20E‐hydroxyecdysone (20E) plays important roles in larval molting and metamorphosis in insects and is also involved in the insect innate immune response. Insect metamorphosis is a highly successful strategy for environmental adaptation and is the most vulnerable stage during which the insect is susceptible to various pathogens. 20E regulates a series of antimicrobial peptides (AMPs) through the immunodeficiency (IMD) pathway activation in Drosophila ; nevertheless, whether other immune pathways are involved in 20E‐regulated insect immunity is unknown. Our previous studies showed that BmMD‐2A is a member of the MD‐2‐related lipid recognition (ML) family of proteins that are involved in the Bombyx mori innate immunity Toll signaling pathway. In this study, we further demonstrate that BmMD‐2A is also positively regulated by 20E, and the BmMD‐2A neutralization experiment suggested that 20E activates some downstream immune effect factors, the AMP genes against Escherichia coli and Staphylococcus aureus , through the regulation of BmMD‐2A in larval metamorphosis, implying that B. mori may use the Toll‐ML signaling pathway to maintain innate immune balance in the larval‐pupal metamorphosis stage, which is a different innate immunity pathway regulated by 20E compared to the IMD pathway in Drosophila .