Diacetoxyscirpenol-induced heterophil extracellular traps contribute to the immune toxicity of liver injury in chickens.

Diacetoxyscirpenol (DAS) is one kind of type A trichothecene mycotoxin which produced by Fusarium species which contaminates agricultural crops and food. DAS attracts particular attention because of the strong toxicity. Heterophil extracellular traps (HETs) is a defense mechanism in the chicken innate immune. In this study, we firstly examine the effects and molecular mechanisms of DAS on HETs release, and then investigate the immune toxicity of DAS-induced HETs on chicken liver. HETs structures were observed by immunofluorescence staining and mechanisms were investigated by fluorescence microplate and Western blot. The results showed DAS triggered HETs formation which consists of chromatin decorated with citrullinated histone 3 (citH3) and elastase. Glycolysis was confirmed to be involved in this process and the inhibitors of NADPH oxidase, ERK, p38 MAPK-signaling pathways and glycolysis significantly decreased HETs formation. Moreover, investigation in vivo showed DAS significantly increased HETs formation in serum and DNase I (a standard degradative agent of HETs) significantly decreased the ALT and AST levels and ameliorated DAS-caused inflammatory cell infiltration of liver. In conclusion, this study proves that DAS-induced HETs formation plays an immune toxicity role in chicken liver injury and these results provide a new therapeutic target for DAS-induced liver injury in chickens.