Vaccine-induced intestinal immunity to ricin toxin in the absence of secretory IgA.

Vaccine-induced intestinal immunity to ricin toxin in the absence of secretory IgA.
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DOI:
10.1016/j.vaccine.2010.11.030
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发表时间:
2011-01-17
期刊:
影响因子:
5.5
通讯作者:
Mantis, Nicholas J.
Mantis, Nicholas J.
中科院分区:
医学3区
文献类型:
--
作者:
Neal, Lori M.;McCarthy, Elizabeth A.;Morris, Carolyn R.;Mantis, Nicholas J.

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RNA N-糖苷酶核糖体失活蛋白(RIP)构成植物和细菌来源的毒素的普遍存在的家族,其包括类别B选择剂蓖麻毒素、相思豆毒素和滋贺毒素。虽然这些毒素是肠上皮细胞死亡和炎症的强效诱导剂,但对这些毒素的粘膜免疫机制知之甚少。在本研究中,我们报告说,分泌型伊加(SIgA)抗体是不需要肠免疫蓖麻毒素,证明了这样一个事实,即小鼠缺乏SIgA,由于突变的多聚免疫球蛋白受体,是不受影响的胃内毒素的挑战后,蓖麻毒素类毒素免疫。此外,肠外给药蓖麻毒素特异性单克隆IgG,直接对蓖麻毒素的酶亚基(RTA)或结合亚基(RTB),野生型小鼠与单克隆IgA具有可比的特异性,在赋予肠道免疫蓖麻毒素一样有效。这些数据与其他人的报告一致,证明通过已知不诱导粘膜抗体应答的途径免疫小鼠(例如,肌内和皮内)足以引起对全身和粘膜蓖麻毒素攻击的保护。
The RNA N-glycosidase ribosome inactivating proteins (RIPs) constitute a ubiquitous family of plant- and bacterium-derived toxins that includes the category B select agents ricin, abrin and shiga toxin. While these toxins are potent inducers of intestinal epithelial cell death and inflammation, very little is known about the mechanisms underlying mucosal immunity to these toxins. In the present study, we report that secretory IgA (SIgA) antibodies are not required for intestinal immunity to ricin, as evidenced by the fact that mice devoid of SIgA, due to a mutation in the polymeric immunoglobulin receptor, were impervious to the effects of intragastric toxin challenge following ricin toxoid immunization. Furthermore, parenteral administration of ricin-specific monoclonal IgGs, directed against either ricin’s enzymatic subunit (RTA) or binding subunit (RTB), to wild type mice were as effective as monoclonal IgAs with comparable specificities in imparting intestinal immunity to ricin. These data are consistent with reports from others demonstrating that immunization of mice by routes known not to induce mucosal antibody responses (e.g., intramuscular and intradermal) are sufficient to elicit protection against both systemic and mucosal ricin challenge.
在聚合物免疫球蛋白受体/分泌成分缺陷的小鼠中,缺乏上皮免疫球蛋白A转运,粘膜泄漏增加。
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