RNAi-Mediated Nucleic Acid Insecticide Weakens the λ-Cyhalothrin Cross-Tolerance in Hyphantria cunea Induced by Cd Stress

Heavy metals are significant environmental pollutants that contribute to widespread contamination. This study demonstrated that Cd transfer through the food chain imparts cross-tolerance to λ-cyhalothrin in Hyphantria cunea larvae. Cd-induced activation of the P450 detoxification system, particularly HcCYP6AE179 and HcCYP9A286, was identified as a critical mechanism for the development of pesticide cross-tolerance in Cd-exposed H. cunea larvae. The dual-luciferase reporter assays, RNAi, and agonist treatment experiment confirmed that HcAhr (Aryl hydrocarbon receptor) upregulated the expression of HcCYP6AE179 and HcCYP9A286. Additionally, H2O2 generation under Cd stress served as a key upstream signal for activating the HcAhr-HcCYP6AE179/HcCYP9A286 detoxification pathway. The nucleic-acid-based pesticides targeting HcAhr, HcCYP6AE179, and HcCYP9A286 exhibited superior stability, biosafety, and gene silencing efficacy. Treatment with these nucleic acid pesticides significantly reduced the tolerance of H. cunea larvae to λ-cyhalothrin in the CK and Cd groups. This work introduces novel approaches for mitigating pesticide cross-tolerance induced by heavy metals.