Glucose negatively affects Nrf2/SKN-1-mediated innate immunity in .

High glucose levels negatively affect immune response. However, the underlying mechanisms are not well understood. Upon infection, the round worm induces multiple gene transcription programs, including the Nrf2/SKN-1-mediated detoxification program, to activate the innate immunity. In this study, we find that high glucose conditions inhibit the SKN-1-mediated immune response to , exacerbate the infection and greatly decrease survival. The effect of glucose shows specificity to SKN-1 pathway, as UPR and UPR that are known to be induced by infection, are not affected. Hyper-activation of SKN-1 by RNAi restores partly the immune response and increases the survival rate in response to . In all, our study reveals a molecular pathway responsible for glucose's negative effect on innate immunity, which could help to better understand diseases associated with hyperglycemia.