Selenium alleviates cadmium-induced immune dysfunction in M1 macrophages by modulating energy metabolism

Cadmium (Cd) is a prevalent environmental pollutant with a destructive impact on most organ systems, including the immune system, while selenium (Se) counteracts the toxicity of Cd to safeguard the immune system. However, the mechanism of Se's protection against Cd toxicity remains obscure, especially regarding the metabolic modulation. In this study, we developed a Cd-exposed M1 macrophage model and investigated the protection and metabolic modulation by Se on Cd-exposed macrophages, utilizing metabolomics and flow cytometry-based energy metabolism analysis. We found that Cd exposure disrupted the morphology and proliferation of M1 macrophages with decreased levels of pro-inflammatory factors like IL-6 and IL-1β et al. A decrease in glucose dependence and glycolytic capacity was observed in Cd-exposed macrophages, together with an increase in mitochondrial dependence and fatty acids and amino acids oxidation. Interestingly, supplementation of Se dramatically reversed the dysfunction of Cd-exposed macrophage by promoting glycolysis, fatty acid biosynthesis, and glutathione metabolism. This study provides metabolic evidence for the protective effect of Se against Cd exposure in the immune system and also sheds light on therapy-oriented prospects of Se in pharmacology.