Isocitrate dehydrogenase-mediated metabolic disorders disrupt active immunization against fungal pathogens in eusocial termites

Abstract

Active immunization is a crucial colony-level pathogen defense to improve the survival of eusocial termites, which limits the lethal effect of biopesticides for termite control. Here, we report a possible strategy for RNAi-mediated metabolic disorders, which causes reduction in insect pathogen defense and might facilitate the foundation of nontoxic and sustainable pest control methods. Isocitrate dehydrogenase (IDH) was significantly upregulated by active immunization in termites, but its regulatory mechanism has yet to be well understood. We found that dsIDH-injected termites exhibited significantly reduced IDH at mRNA and protein levels and altered levels of isocitrate and NADH, indicating the impaired NAD+-IDH reaction. IDH-silenced termites displayed metabolic disorders, which was implied by significant changes in several metabolites from the carbohydrates and amino acids. When grooming toward fungus-exposed termites, IDH-silenced nestmates showed a significant upregulation of four apoptosis-related genes and caspase 3 activity, and hence the significantly increased rate of apoptosis. These physiological changes led to more apoptotic cell death in different body parts of the nestmates. In particular, more apoptotic cells increased disease susceptibility of the nestmates as revealed by growth of the significantly increased number of colony-forming units from dissected gut contents. Furthermore, the IDH-silenced nestmates exhibited lower antifungal activity and higher mortality, suggesting that IDH downregulation disrupted active immunization against fungal pathogens in termites. These findings illustrated the metabolic regulation of active immunization and provide a sound foundation for enhancing the impact of biopesticides by reducing the pathogen defense of hosts.