Quercetin mitigated LPS-induced PANoptosis in the bursa of Fabricius via the cGAS/STING signaling pathway in broilers.

Abstract

Quercetin (QUE), a natural bioflavonoid with anti-inflammatory and antioxidant properties, regulates immune organ function by enhancing antioxidant capacity and maintaining mitochondrial homeostasis. This study aims to explore whether QUE can mitigate lipopolysaccharide (LPS)-induced PANoptosis in broilers bursal cells via cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. In vivo, White Leghorn chickens were assigned to Control, QUE (10 mg/kg gavage), LPS (0.15 mg/kg intraperitoneal injection), and LPS+QUE groups. In vitro, brolier lymphoma cells (DT40) were treated with LPS (40 μg/mL), QUE (10 μM), or their combination; STING agonist MSA-2 (2 μM) was used to verify pathway involvement. Hematoxylin-Eosin (H&E) staining, TUNEL assay, immunofluorescence, reactive oxygen species (ROS) detection, antioxidant index assays, quantitative real-time PCR (qRT-PCR), and Western blot (WB) were employed to detect factors related to PANoptosis, inflammation, mitochondrial dynamics, mitochondrial metabolism and the cGAS/STING signaling pathway. Results demonstrated that QUE effectively mitigated LPS-induced oxidative stress, mitochondrial dynamics imbalance, and mitochondrial metabolic dysfunction in broiler bursal cells and DT40 cells. Consequently, QUE reduced the release of mitochondrial DNA (mtDNA) into the cytoplasm, suppressed the activation of the cGAS/STING signaling pathway, and ultimately attenuated the occurrence of PANoptosis and inflammatory responses. This study confirms that QUE exerts a protective effect against LPS-induced PANoptosis via cGAS/STING pathway in the broiler bursa of Fabricius, thereby providing a novel theoretical basis for the application of QUE as a green feed additive. Notably, this finding underscores the potential of QUE as a natural and effective alternative to traditional antibiotics in animal feed, which is of great significance for reducing antibiotic dependence and facilitating the sustainable development of the poultry farming industry.