Verdin-Terán S L, Vilches-Flores A, Moreno-Fierros L
Inmunidad en Mucosas, Unidad de Biomedicina, FES-Iztacala, Universidad Nacional Autónoma de México, Av. de los Barrios 1 Col. Los Reyes Iztacala Tlalnepantla, Edo. de México, México.
Scand J Immunol. 2009 Dec;70(6):596-607. doi: 10.1111/j.1365-3083.2009.02332.x.
We have shown that Cry1Ac protoxin from Bacillus thuringiensis is a potent mucosal and systemic immunogen with adjuvant properties. Interestingly, we have observed that Cry1Ac preferentially induces high specific IgG responses in intestinal fluid when it is intraperitoneally administered to mice; therefore, in the present study, we used this protocol, as a model to address the influence of systemic immunization on the induction of the intestinal IgG response. The data shown indicate that upon intraperitoneal immunization with Cry1Ac, significant intestinal specific IgG cell responses were produced in the lamina propria, accompanied by an increased frequency of intestinal IgG+ lymphocytes and epithelial cells containing IgG. Considering that FcRn is the receptor responsible for the transport of IgG in neonatal intestinal epithelia, but it is developmentally downregulated in the rodent intestine, we analysed whether upon intestinal IgG induction, FcRn mRNA expression was induced in intestinal epithelial cells, of adult mice. Whereas in intestinal epithelia of unimmunized adult mice FcRn mRNA was not detected, in Cry1Ac immunized mice it was expressed, although the level was lower in comparison with that found in neonatal epithelia. Then using flow cytometry and immunofluorescence we confirmed that the expression of the protein FcRn was induced in the intestines of adult immunized mice especially in the large intestine. Finally, we found that Cry1Ac also increased FcRn expression in isolated intestinal epithelial cells stimulated in vitro. The outcomes suggest that the expression of FcRn in intestinal epithelium might be reactivated upon immunization, and possibly facilitate IgG transport.
我们已经证明,来自苏云金芽孢杆菌的Cry1Ac原毒素是一种具有佐剂特性的强效黏膜和全身免疫原。有趣的是,我们观察到,当将Cry1Ac腹腔注射给小鼠时,它优先在肠液中诱导产生高特异性IgG反应;因此,在本研究中,我们采用该方案作为模型来探讨全身免疫对肠道IgG反应诱导的影响。所示数据表明,用Cry1Ac进行腹腔免疫后,在固有层中产生了显著的肠道特异性IgG细胞反应,同时肠道IgG+淋巴细胞和含有IgG的上皮细胞的频率增加。鉴于FcRn是负责新生儿肠道上皮中IgG转运的受体,但它在啮齿动物肠道中会随着发育而下调,我们分析了在诱导肠道IgG时,成年小鼠肠道上皮细胞中FcRn mRNA表达是否会被诱导。在未免疫的成年小鼠肠道上皮中未检测到FcRn mRNA,而在Cry1Ac免疫的小鼠中它有表达,尽管与新生儿上皮中的水平相比要低。然后,我们使用流式细胞术和免疫荧光证实,在成年免疫小鼠的肠道中,尤其是在大肠中,诱导了FcRn蛋白的表达。最后,我们发现Cry1Ac还增加了体外刺激的分离肠道上皮细胞中FcRn的表达。这些结果表明,免疫后肠道上皮中FcRn的表达可能会被重新激活,并可能促进IgG的转运。