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

ABSTRACT: High glucose levels negatively affect immune response. However, the underlying mechanisms are not well understood. Upon infection, the round worm C. elegans 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 Salmonella typhimurium, exacerbate the infection and greatly decrease survival. The effect of glucose shows specificity to SKN-1 pathway, as UPR^mit and UPR^ER that are known to be induced by infection, are not affected. Hyper-activation of SKN-1 by wdr-23 RNAi restores partly the immune response and increases the survival rate in response to S. typhimurium. 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.

SUBMITTER: Li L

PROVIDER: S-EPMC6286829 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Li Le L Chen Yi Y Chenzhao Changchi C Fu Shuxiang S Xu Qumiao Q Zhao Jinfeng J

Aging 20181101 11

High glucose levels negatively affect immune response. However, the underlying mechanisms are not well understood. Upon infection, the round worm C. elegans 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 Salmonella typhimurium, exacerbate the infection and greatly decrease survival. The effect of ...[more]

PMID: 30442878

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