Vatzia Eleni, Pierron Alix, Hoog Anna Maria, Saalmüller Armin, Mayer Elisabeth, Gerner Wilhelm
Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria.
BIOMIN Research Center, Tulln, Austria.
Front Immunol. 2020 Aug 13;11:2009. doi: 10.3389/fimmu.2020.02009. eCollection 2020.
Deoxynivalenol (DON) is a mycotoxin that frequently contaminates the feed of farm animals. Pigs with their monogastric digestive system are in particular sensitive to DON-contaminated feed. At high concentrations, DON causes acute toxic effects, whereas lower concentrations lead to more subtle changes in the metabolism. This applies in particular to the immune system, for which immunosuppressive but also immunostimulatory phenomena have been described. Research in human and rodent cell lines indicates that this may be partially explained by a binding of DON to the ribosome and subsequent influences on cell signaling molecules like mitogen-activated protein kinases. However, a detailed understanding of the influence of DON on functional traits of porcine immune cells is still lacking. In this study, we investigated the influence of DON on transcription factor expression and cytokine production within CD4, CD8, and γδ T cells . At a DON concentration, that already negatively affects proliferation after Concanavalin A stimulation (0.8 μM) an increase of T-bet expression in CD4 and CD8 T cells was observed. This increase in T-bet expression coincided with elevated levels of IFN-γ and TNF-α producing T-cell populations. Increases in T-bet expression and cytokine production were found in proliferating and non-proliferating T cells, although increases were more prominent in proliferating cell subsets. Differently, IL-17A production by CD4 T cells was not influenced by DON. In addition, frequencies of regulatory T cells and their expression of Foxp3 were not affected. In γδ T cells, GATA-3 expression was slightly reduced by DON, whereas T-bet levels were only slightly modulated and hence IFN-γ, TNF-α, or IL-17A production were not affected. Our results show for the single-cell level that DON has the capacity to modulate the expression of transcription factors and related cytokines. In particular, they suggest that for CD4 and CD8 T cells, DON can drive T-cell differentiation into a pro-inflammatory type-1 direction, probably depending on the already prevailing cytokine milieu. This could have beneficial or detrimental effects in ongoing immune responses to infection or vaccination.
脱氧雪腐镰刀菌烯醇（DON）是一种经常污染农场动物饲料的霉菌毒素。具有单胃消化系统的猪对受DON污染的饲料特别敏感。高浓度时，DON会引起急性毒性作用，而较低浓度则会导致新陈代谢发生更细微的变化。这尤其适用于免疫系统，已有文献描述了其免疫抑制和免疫刺激现象。对人类和啮齿动物细胞系的研究表明，这可能部分是由于DON与核糖体结合，随后对丝裂原活化蛋白激酶等细胞信号分子产生影响。然而，仍缺乏对DON对猪免疫细胞功能特性影响的详细了解。在本研究中，我们研究了DON对CD4、CD8和γδ T细胞内转录因子表达和细胞因子产生的影响。在一个已经对刀豆球蛋白A刺激后的增殖产生负面影响的DON浓度（0.8μM）下，观察到CD4和CD8 T细胞中T-bet表达增加。T-bet表达的这种增加与产生IFN-γ和TNF-α的T细胞群体水平升高相一致。在增殖和非增殖T细胞中均发现T-bet表达和细胞因子产生增加，尽管在增殖细胞亚群中增加更为显著。不同的是，CD4 T细胞产生的IL-17A不受DON影响。此外，调节性T细胞的频率及其Foxp3表达不受影响。在γδ T细胞中，DON使GATA-3表达略有降低，而T-bet水平仅略有调节，因此IFN-γ、TNF-α或IL-17A的产生不受影响。我们的结果在单细胞水平上表明，DON有能力调节转录因子和相关细胞因子的表达。特别是，它们表明对于CD4和CD8 T细胞，DON可以驱动T细胞分化为促炎的1型方向，这可能取决于已经存在的细胞因子环境。这可能对正在进行的感染或疫苗免疫反应产生有益或有害的影响。
