发表论文

Manganese potentiates lipopolysaccharide-induced innate immune responses and septic shock

作者:  来源:10.1016/j.ijbiomac.2023.123202  发布日期:2023-03-01  浏览次数:

Manganese potentiates lipopolysaccharide-induced innate immune responses and septic shock

Yanchao Gu, Jingjing Tang, Fuhua Zhang, Yichen Qu, Min Zhao, Mengyuan Li, Zhen Xie, Xiao Wang, Li Song, Zhengfan Jiang, Yao Wang, Xihui Shen and Lei Xu

International Journal of Biological Macromolecules

https://doi.org/10.1016/j.ijbiomac.2023.123202

Abstract

Divalent metal ions such as magnesium (Mg2+), manganese (Mn2+), and zinc (Zn2+) play important roles in regulating innate immune responses. Lipopolysaccharide stimulation led to increased intracellular Mn and Zn in macrophages. However, the effect of those metal ions in regulating lipopolysaccharide-induced innate immune responses remains unclear. Here, we uncovered that both Mn2+ and Zn2+ have immunostimulatory effects, which could potentiate the lipopolysaccharide-induced expression of interferon-stimulated genes (ISGs), cytokines and pro-inflammatory genes in a dose-dependent manner. Enhancement of lipopolysaccharide-induced innate immune gene expression by Mn2+ varies between 10 % and 900 %. Conversely, the chelating of Mn2+ almost totally diminished Mn2+-enhanced lipopolysaccharide-induced gene expression. In addition, Mn2+ exerted its ability to potentiate LPS-induced innate immune gene expression regardless of slight pH changes. Importantly, we found that Mn2+ potentiates lipopolysaccharide-induced immune responses independent of TLR4 but partially relies on cGAS-STING pathway. Further in vivo study showed that colloidal Mn2+ salt (Mn jelly [MnJ]) pretreatment exacerbated lipopolysaccharide-induced septic shock and mice death. In conclusion, we demonstrated that Mn2+ plays an essential role in boosting lipopolysaccharide-induced innate immune responses. These findings greatly expand the current understanding of the immunomodulatory potential of divalent metal Mn2+ and may provide a potential therapeutic target to prevent excessive immune responses.