Immunotoxicity of aflatoxin B1: Impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression
Immunotoxicity of aflatoxin B1: Impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression
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DOI：
10.1016/j.taap.2008.04.004
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发表时间：
2008-09-01
影响因子：
3.8
通讯作者：
Oswald, Isabelle P.
中科院分区：
文献类型：
--
作者：
Meissonnier, Guylaine M.;Pinton, Philippe;Oswald, Isabelle P.
黄曲霉毒素B1 （AFB1）是一种由黄曲霉或寄生蜂产生的霉菌毒素，是食品和饲料中常见的污染物。这种毒素具有肝毒性和免疫毒性。本研究分析了AFB1对猪体液和细胞反应的影响，并研究了所观察到的免疫调节是否通过干扰细胞因子的表达而产生。试验28 d，分别饲喂对照饲粮和添加385、867和1807 μ g纯AFB1/kg饲料的饲粮。在第4天和第15天分别接种卵清蛋白。通过观察血液中黄曲霉毒素-白蛋白加合物的剂量反应，证实了AFB1暴露对体液免疫没有重大影响，通过血浆中总IgA、IgG和IgM以及抗卵清蛋白IgG的浓度来测量。毒素暴露不损害淋巴细胞的有丝分裂反应，但延迟和降低了它们对疫苗抗原的特异性增殖，表明暴露于AFB1的猪的淋巴细胞活化受损。实时荧光定量PCR检测脾组织中促炎因子（tnf - α、IL-1 β、IL-6、ifn - γ）和调节因子（IL-10）的表达水平。暴露于最高剂量AFB1的猪脾脏中5种细胞因子均显著上调。在中等剂量暴露的猪中，IL-6表达增加，ifn - γ和IL-10也有增加的趋势。此外，我们证明IL-6在体外损害了抗原诱导的淋巴细胞增殖，而不是免疫卵清蛋白的对照猪的有丝分裂诱导的增殖。这些结果表明，AFB1饮食暴露会降低细胞介导的免疫，同时诱导炎症反应。这些免疫反应的损伤可能参与疫苗接种方案的失败和暴露于AFB1的猪对感染的易感性增加。(C) 2008爱思唯尔公司版权所有。
Aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus flavus or A. parasiticus, is a frequent contaminant of food and feed. This toxin is hepatotoxic and immunotoxic. The present study analyzed in pigs the influence of AFB1 on humoral and cellular responses, and investigated whether the immunomodulation observed is produced through interference with cytokine expression. For 28 days, pigs were fed a control diet or a diet contaminated with 385, 867 or 1807 mu g pure AFB1/kg feed. At days 4 and 15, pigs were vaccinated with ovalbumin. AFB1 exposure, confirmed by an observed dose-response in blood aflatoxin-albumin adduct, had no major effect on humoral immunity as measured by plasma concentrations of total IgA, IgG and IgM and of anti-ovalbumin IgG. Toxin exposure did not impair the mitogenic response of lymphocytes but delayed and decreased their specific proliferation in response to the vaccine antigen, suggesting impaired lymphocyte activation in pigs exposed to AFB1. The expression level of pro-inflammatory (TNF-alpha, IL-1 beta, IL-6, IFN-gamma) and regulatory (IL-10) cytokines was assessed by real-time PCR in spleen. A significant up-regulation of all 5 cytokines was observed in spleen from pigs exposed to the highest dose of AFB1. In pigs exposed to the medium dose, IL-6 expression was increased and a trend towards increased IFN-gamma and IL-10 was observed. In addition we demonstrate that IL-6 impaired in vitro the antigenic- but not the mitogenic-induced proliferation of lymphocytes from control pigs vaccinated with ovalbumin. These results indicate that AFB1 dietary exposure decreases cell-mediated immunity while inducing an inflammatory response. These impairments in the immune response could participate in failure of vaccination protocols and increased susceptibility to infections described in pigs exposed to AFB1. (C) 2008 Elsevier Inc. All rights reserved.