Phytochemical Flavone Confers Broad-Spectrum Tolerance to Insecticides in Spodoptera litura by Activating ROS/CncC-Mediated Xenobiotic Detoxification Pathways

Tolerance
to chemical insecticides can be driven by the necessity
of herbivorous insects to defend against host plant-produced phytochemicals.
However, how the phytochemicals are sensed and further transduced
into a defense response associated with insecticide tolerance is poorly
understood. Herein, we show that pre-exposure to flavone, a flavonoid
phytochemical, effectively enhanced larval tolerance to multiple synthetic
insecticides and elevated detoxification enzyme activities in Spodoptera litura. RNA-Seq analysis revealed that
flavone induced a spectrum of genes spanning phase I and II detoxification
enzyme families, as well as two transcription factors Cap “n”
collar isoform C (CncC) and its partner small muscle aponeurosis fibromatosis
(MafK). Knocking down of CncC by RNA interference
suppressed flavone-induced detoxification gene expression and rendered
the larvae more sensitive to the insecticides. Flavone exposure elicited
a reactive oxygen species (ROS) burst, while scavenging of ROS inhibited
CncC-mediated detoxification gene expression and suppressed flavone-induced
detoxification enzyme activation. Metabolome analysis showed that
the ingested flavone was mainly converted into three flavonoid metabolites,
and only 3-hydroxyflavone was found to affect the ROS/CncC pathway-mediated
metabolic detoxification. These results indicate that the ROS/CncC
pathway is an important route driving detoxification gene expression
responsible for insecticide tolerance after exposure to the phytochemical
flavone.