Quercetin alleviates LPS-induced inflammation and immunosuppression in broiler spleen via regulating the mtDNA/cGAS/STING axis

Quercetin has significant biological activities in anti-oxidation, anti-inflammation, immunomodulation and anti-cancer. Lipopolysaccharide, a key factor in inducing sepsis, is widely used to simulate the pathological process of endotoxemia. The study sought to elucidate the ameliorative role of quercetin and its underlying mechanisms mitigate lipopolysaccharide-induced splenic damage in broiler. The results showed that lipopolysaccharide stimulation caused splenic tissues edema and inflammatory infiltration, increased Reactive Oxygen Species levels, suppressed antioxidant enzyme activities, and led to accumulation of oxidative stress products in broiler spleen. Concurrently, LPS exposure inhibited the expression of mitochondrial respiratory chain complex I∼V and exacerbated mitochondrial fission. Furthermore, the increased expression of pyroptosis-related genes, pro-inflammatory and anti-inflammatory factors, and the decreased concentration of IgG, IgA and IgM in serum indicated that lipopolysaccharide exposure induced Pyroptosis, inflammation and immunosuppression in broiler spleen. However, quercetin treatment effectively inhibited mitochondrial DNA/Cyclic GMP-AMP Synthase/stimulator of interferon gene signaling pathway and alleviated these pathological changes. In vitro experiments further confirmed these ameliorative effects, which could be counteracted by the oxidative stress inducer H₂O₂ and STING agonist G10. In conclusion, quercetin ameliorates lipopolysaccharide-induced splenic inflammation and immunosuppression in broiler by enhancing antioxidant capacity and suppressing mtDNA/cGAS/STING axis activation.