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.

Andalusian Research Institute in Data Science and Computational Intelligence University of Granada 18071 Granada Spain

College of Life Science Yangtze University Jingzhou 434025 China

College of Physical Education and Health Chongqing College of International Business and Economics Chongqing 401520 China

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Králové 500 03 Czech Republic

MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 China

National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues Huazhong Agricultural University Wuhan China

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