Quercetin restores respiratory mucosal barrier dysfunction in Mycoplasma gallisepticum-infected chicks by enhancing Th2 immune response.

Abstract

Mycoplasma gallisepticum (MG) has long been a pathogenic microorganism threatening the global poultry industry. Previous studies have demonstrated that the mechanism by which quercetin (QUE) inhibits the colonization of MG in chicks differs from that of antibiotics. However, the molecular mechanism by which QUE facilitates the clearance of MG remains unclear. The aim of this study was to investigate the molecular mechanism of MG clearance by QUE, with the expectation of providing new options for the treatment of MG. A model of MG infection in chicks and MG-induced M1 polarization in HD-11 cells were established. The mechanism of QUE clearance of MG was investigated by evaluating the relationship between tracheal mucosal barrier integrity, antibody levels, Th1/Th2 immune balance and macrophage metabolism and M1/M2 polarization balance. Furthermore, network pharmacology and molecular docking techniques were employed to explore the potential molecular pathways connecting QUE, M2 polarization, and fatty acid oxidation (FAO). The findings indicate that QUE remodels tracheal mucosal barrier function by regulating tight junctions and secretory immunoglobulin A (sIgA) expression levels. This process entails the regulatory function of QUE on the Th1/Th2 immune imbalance that is induced by MG infection in the tracheal mucosa. Moreover, QUE intervention impeded the M1 polarization of HD-11 cells induced by MG infection, while simultaneously promoting M2 polarization through the induction of FAO. Conversely, inhibitors of the FAO pathway impede this effect. The results of computer network analysis suggest that QUE may induce FAO via the PI3K/AKT pathway to promote M2 polarization. Notably, inhibition of the PI3K/AKT pathway was found to effectively inhibit M2 polarization in HD-11 cells, while having a limited effect on FAO. QUE promotes M2 polarization of HD-11 cells to enhance Th2 immune response through FAO and PI3K/AKT pathways, thereby restoring tracheal mucosal barrier function and ultimately inhibiting MG colonization.