Li Le, Chen Yi, Chenzhao Changchi, Fu Shuxiang, Xu Qumiao, Zhao Jinfeng
Key Laboratory of Nanobiological Technology of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, China.
Department of Laboratory Medicine, Xiangya Medical School, Central South University, Changsh, Changsha 410013, China.
Aging (Albany NY). 2018 Nov 15;10(11):3089-3103. doi: 10.18632/aging.101610.
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.
高血糖水平会对免疫反应产生负面影响。然而，其潜在机制尚未完全明确。受到感染时，蛔虫会诱导多种基因转录程序，包括由Nrf2/SKN-1介导的解毒程序，以激活先天免疫。在本研究中，我们发现高糖条件会抑制SKN-1介导的对[感染源未明确]的免疫反应，加剧感染并显著降低存活率。葡萄糖的这种作用对SKN-1途径具有特异性，因为已知由感染诱导的未折叠蛋白反应（UPR）不受影响。通过RNA干扰过度激活SKN-1可部分恢复免疫反应，并提高对[感染源未明确]的存活率。总之，我们的研究揭示了一条负责葡萄糖对先天免疫产生负面影响的分子途径，这有助于更好地理解与高血糖相关的疾病。
