Department of Pathobiology, Institute of Immunology, University of Veterinary Medicine, Vienna, Austria.
dsm-firmenich, Animal Nutrition and Health R&D Center, Tulln, Austria.
Front Immunol. 2024 Feb 21;15:1338937. doi: 10.3389/fimmu.2024.1338937. eCollection 2024.
The mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), produced by fungi, are frequently found in the cereal-rich diet of pigs and can modulate the immune system. Some enzymes or bacteria present in the digestive tract can de-epoxydize DON to deepoxy-deoxynivalenol (DOM-1) and biotransform ZEN into hydrolyzed ZEN (HZEN). The effects of these metabolites on immune cells, particularly with respect to the vaccine responses, are poorly documented. The aim of this study was to address the impact of DON and ZEN and their respective derivatives, on proliferation, and antibody production of porcine B cells .
Peripheral blood mononuclear cells (PBMCs), isolated from healthy pigs, were stimulated with the Toll-like receptor (TLR) 7/8-agonist Resiquimod (R848) or the TLR/1/2-agonist Pam3Cys-SKKKK in combination with DON [0.1-1.6 µM] or DOM-1 [1.6 µM and 16 µM] and ZEN [2.5-40 µM] or HZEN [40 µM].
A strong decrease in B-cell proliferation was observed at DON concentrations equal to or exceeding 0.8 µM and at ZEN concentrations equal to or exceeding 20 µM. Treatment with 1.6 µM DON or 40 µM ZEN led to almost a complete loss of live CD79α B cells. Moreover, CD21 expression of proliferating IgG and IgM B-cell subsets was decreased at DON concentrations equal to and exceeding 0.4 µM and at ZEN concentrations equal to or exceeding 10 µM. ELISpot assays revealed a decrease of IgG-secreting B cells at concentrations of and exceeding 0.4 µM and at ZEN concentrations equal to and exceeding 10 µM. ELISA assays showed a decrease of IgM, IgG, and IgA secretion at concentrations equal to or exceeding 0.4 µM DON. ZEN reduced IgM secretion at 20-40 µM (both R848 and Pam3Cys-SKKKK), IgG secretion at 40 µM (both R848 and Pam3Cys-SKKKK) and IgA secretion at 20-40 µM.
Our experiments show that while DON and ZEN impair immunoglobulin production and B-cell proliferation, this effect is abrogated by HZEN and DOM-1.
真菌产生的霉菌毒素脱氧雪腐镰刀菌烯醇（DON）和玉米赤霉烯酮（ZEN）经常存在于富含谷物的猪饲料中，并能调节免疫系统。消化道中存在的一些酶或细菌可以将 DON 脱环氧化为去氧雪腐镰刀菌烯醇（DOM-1），并将 ZEN 生物转化为水解玉米赤霉烯酮（HZEN）。这些代谢物对免疫细胞的影响，特别是对疫苗反应的影响，记录甚少。本研究旨在探讨 DON 和 ZEN 及其各自衍生物对猪 B 细胞增殖和抗体产生的影响。
从健康猪中分离外周血单核细胞（PBMCs），用 Toll 样受体（TLR）7/8 激动剂 Resiquimod（R848）或 TLR/1/2 激动剂 Pam3Cys-SKKKK 与 DON[0.1-1.6 μM]或 DOM-1[1.6 μM 和 16 μM]和 ZEN[2.5-40 μM]或 HZEN[40 μM]联合刺激。
当 DON 浓度等于或高于 0.8 μM 且 ZEN 浓度等于或高于 20 μM 时，B 细胞增殖明显下降。用 1.6 μM DON 或 40 μM ZEN 处理，几乎完全丧失了活的 CD79α B 细胞。此外，当 DON 浓度等于或高于 0.4 μM 且 ZEN 浓度等于或高于 10 μM 时，增殖 IgG 和 IgM B 细胞亚群的 CD21 表达减少。ELISpot 检测显示，当 DON 浓度等于或高于 0.4 μM 且 ZEN 浓度等于或高于 10 μM 时，IgG 分泌 B 细胞减少。ELISA 检测显示，当 DON 浓度等于或高于 0.4 μM 时，IgM、IgG 和 IgA 的分泌减少。ZEN 降低了 20-40 μM（R848 和 Pam3Cys-SKKKK 均）时的 IgM 分泌，40 μM（R848 和 Pam3Cys-SKKKK 均）时的 IgG 分泌和 20-40 μM 时的 IgA 分泌。
我们的实验表明，虽然 DON 和 ZEN 会损害免疫球蛋白的产生和 B 细胞的增殖，但 HZEN 和 DOM-1 可以阻断这种作用。
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