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Research Paper|Volume 10, Issue 11|pp 3089—3103

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

Le Li1, Yi Chen2, Changchi Chenzhao3, Shuxiang Fu4, Qumiao Xu5, Jinfeng Zhao1
  • 1Key Laboratory of Nanobiological Technology of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, China
  • 2Department of Laboratory Medicine, Xiangya Medical School, Central South University, Changsh, Changsha 410013, China
  • 3Xinxiang Medical University, Hongqi District, 453003 Xinxiang, China
  • 4Forevertek Biotechnology Co.,Ltd, Building M0, Oversea Graduate Park National High-tech Industrial Zone, Changsha 10003, China
  • 5BGI-Shenzhen, BeiShan Industrial Zone, Yantian District, Shenzhen, Guangdong 518083, China

* * Equal contribution

Received: June 5, 2018Accepted: October 19, 2018Published: November 15, 2018
https://doi.org/10.18632/aging.101610

Copyright: © 2018 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 UPRmit and UPRER 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.