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Abstract
Trichothecene mycotoxins have a strong immunosuppressive effect, which may even escape
host immune surveillance and damage the immune repair to show an "immune evasion"
effect. Increasing lines of evidence have shown that hypoxia and hypoxia-inducible
factors (HIFs) are key mediators of trichothecenes, and these toxins appear to be
closely related to the "immune evasion" mechanisms. Therefore, we used RAW264.7 cell
model to explore the association of T-2 toxins with "immune evasion" process and hypoxia,
as well as their cross-linking effects induced by T-2 toxin. Our results showed that
HIF-1α is an important toxicity target of T-2 toxin, which could induce intracellular
hypoxia. T-2 toxin induced an "immune evasion" process by activating the PD-1/PD-L1
signaling pathway. Interestingly, when HIF-1α activation was blocked, the "immune
evasion" process regulated by PD-1/PD-L1 signaling was activated, resulting in the
cells damage, suggesting that hypoxia induced by T-2 toxin plays a protective role
for RAW264.7 cell damage. Thus, our work shows that HIF-1α inhibits T-2 toxin-mediated
"immune evasion" process by negatively regulating PD-1/PD-L1signaling. This study
contributes to a better understanding of the immunotoxicity mechanism of trichothecenes.