The release of FB1-induced heterophil extracellular traps in chicken is dependent on autophagy and glycolysis

Abstract

Fumonisin B₁ (FB₁), a worldwide contaminating mycotoxin produced by Fusarium, poses a great threat to the poultry industry. It was reported that extracellular traps could be induced by FB₁ efficiently in chickens. However, the relevance of autophagy and glycolysis in FB₁-triggered heterophil extracellular trap (HET) formation is unclear. In this study, immunostaining revealed that FB₁-induced HETs structures were composed of DNA coated with histones H3, and elastase, and that heterophils underwent LC3B-related autophagosome formation assembly driven by FB₁. Western blotting showed that FB₁ downregulated the phosphorylated phosphoinositide 3-kinase3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin complex 1 (mTORC1) axis and raised the AMP-activated kinase α (AMPKα) activation protein. Furthermore, rapamycin- and 3-Methyladenine (3-MA)-treatments modulated FB₁-triggered HET formation according to the pharmacological analysis. Further studies on energy metabolism showed that glucose/lactate transport and glycolysis inhibitors abated FB₁-induced HETs. These results showed that FB₁-induced HET formation might interact with the autophagy process and relied on glucose/monocarboxylic acid transporter 1 (MCT1) and glycolysis, reflecting chicken's early innate immune responses against FB₁ intake.

Keywords: autophagy; chicken; fumonisin B(1); glycolysis; heterophil extracellular traps.