霍乱弧菌神经氨酸作为口服变态反应免疫疗法免疫调节剂的特性研究

Characterization of Vibrio cholerae neuraminidase as an immunomodulator for novel formulation of oral allergy immunotherapy

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中文摘要:研究评估了霍乱弧菌神经氨酸(NA)作为PLGA微粒(MPs)的一种新型上皮靶向分子在提高粘膜变态反应免疫疗法方面的作用,并与已有的上皮细胞靶向凝集素小麦胚芽凝集素(WGA)和橙黄网胞盘菌凝集素(AAL)进行比较。结果所有的靶向靶向因子均能与Caco-2细胞结合,但只有NA与α-L海藻糖和单唾液酸神经节苷酯-1具有较高的结合特异性。在M-细胞共培养模型中,NA-MPs经上皮摄取的比例增加。NA和NA-MPs能够诱导小鼠脾细胞产生高浓度的IFN-g 和IL10,诱导Caco-2中CCL20的表达。NA-MPs重复口服会形成一种新的经过调节的变应原特异性免疫反应。总而言之,NA与其它靶向因子相比能够增强M细胞特异性。NA功能性MPs诱导产生一种Th1和T-调控性驱动免疫反应,且避免了变态反应细胞的活化,作为一种新型的口服变态反应疗法具有一定的应用前景。
 
外文摘要:To improve current mucosal allergen immunotherapy Vibrio cholerae neuraminidase (NA) was evaluated as a novel epithelial targeting molecule for functionalization of allergen-loaded, poly(D,L-lactide-co-glycolide) (PLGA) microparticles (MPs) and compared to the previously described epithelial targeting lectins wheat germ agglutinin (WGA) and Aleuria aurantia lectin (AAL). All targeters revealed binding to Caco-2 cells, but only NA had high binding specificity to alpha-L fucose and monosialoganglioside-1. An increased transepithelial uptake was found for NA-MPs in a M-cell co-culture model. NA and NA-MPs induced high levels of IFN-gamma and IL10 in naive mouse splenocytes and CCL20 expression in Caco-2. Repeated oral gavage of NA-MPs resulted in a modulated, allergen-specific immune response. In conclusion, NA has enhanced M-cell specificity compared to the other targeters. NA functionalized MPs induce a Th1 and T-regulatory driven immune response and avoid allergy effector cell activation. Therefore, it is a promising novel, orally applied formula for allergy therapy.
外文关键词:Neuraminidase; M-cell; Oral application; PLGA-microparticles; AAL; WGA
作者:Diesner, SC;Bergmayr, C;Wang, XY;Heiden, D;Exenberger, S;Roth-Walter, F;Starkl, P;Ret, D;Pali-Scholl, I;Gabor, F;Untersmayr, E
作者单位:澳大利亚维也纳医科大学
期刊名称:CLINICAL IMMUNOLOGY
期刊影响因子:3.557
出版年份:2018
出版刊次:8
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  1. 编译服务:动物支原体学
  2. 编译者:程金花
  3. 编译时间:2018-07-31