T-2 toxin triggers immune toxicity by enhancing glycolysis and activating TLR2/4-MAPK signaling pathways in bovine.

T-2 toxin, a potent immunotoxic trichothecene, has widely existed in the environment and grains, and been recognized for its detrimental effects on both animal and human immune systems. The recent elucidation of extracellular traps (ETs) as an innate immune response has highlighted their role in the release of heterophil extracellular traps (HETs) in chickens upon T-2 toxin exposure. However, the interplay between T-2 toxin and macrophage extracellular traps (METs) in bovine remains unexplored. In this study, we employed Pico Green staining to demonstrate that T-2 toxin induces METs formation in a dose-dependent manner. Subsequent immunofluorescence analysis confirmed the structures of METs, characterized by a DNA backbone co-localized with citrullinated histone 3 (citH3) and elastase. Additionally, our findings revealed a significant escalation in reactive oxygen species (ROS) levels (P < 0.001) during T-2 toxin-induced METs formation, suggesting the ROS-dependent mechanism of this process. Inhibitor studies further delineated the reliance of T-2 toxin -induced METs on NADPH oxidase activity and the activation of extracellular signal-regulated kinases (ERK) and p38 signaling pathways. Moreover, our results suggest a synergistic relationship between glycolysis and Toll-like receptor (TLR) signaling in METs formation induced by T-2 toxin. Collectively, this study presents novel evidence that T-2 toxin is capable of eliciting METs formation in bovine macrophages, potentially offering novel strategies for mitigating tissue damage and addressing food safety concerns associated with chronic T-2 toxin exposure.