Protection against gastrointestinal nematode infection by sialic acid linkaged mucin

我们的项目的目标是更好地了解对胃肠道线虫感染的保护机制。我们采用巴西日本圆线虫感染的小鼠模型，这是胃肠道线虫感染的代表性实验模型之一。在本研究中，我们首先试图交换信息的保护机制分别显示从大鼠和小鼠系统。自1930年以来，人们一直在研究大鼠的排出机制，并提出了两个步骤。然后，我们研究了两步理论在大鼠中也适用于小鼠。结果表明，第一步，免疫介导的损害蠕虫，是不必要的小鼠驱逐成年N。brasiliensis从小肠中分离，第二步，非特异性粘膜反应是关键（Ishiwata et al.2002）。此外，我们认为第二步是Stat6依赖的杯状细胞反应。两种小鼠模型都暗示了CD4+细胞对于排出是重要的。小鼠系统最近显示，成年N.巴西驱逐我们接下来通过凝集素组织化学检查小鼠杯状细胞粘蛋白的特征性变化。结果表明，杯状细胞粘蛋白中的唾液酸键与成虫的发育有关。brasiliensis驱逐（Ishiwata et al. submitted）.此外，表达的酶，唾液酸转移酶，上调的时间蠕虫驱逐或外源性IL-13治疗诱导成虫驱逐scid小鼠。综上所述，我们提出了一个保护机制，对N。巴西丝虫感染小鼠的情况如下：CD 4+细胞释放IL-13-> IL-13与杯状细胞上的IL-4受体结合-> Stat6激活->唾液酸转移酶表达上调->唾液酸与粘蛋白的连接->成虫驱逐。

The goal of our project is to get a better understanding on the protective mechanisms against gastrointestinal nematode infection. We employ Nippostrongylus brasiliensis-infected murine model that is one of the representative experimental models of gastrointestinal nematode infection. In this study, we firstly tried to interchange the information on protective mechanisms shown separately from rats- and mice-system. Expulsion mechanism in rats has been studied since 1930 and proposed to have two steps. Then we examined the two step theory in rats is also applicable in mice. Results suggested that first step, immune-mediated damage to the worms, is not essential for mice to expel adult N. brasiliensis from small intestine and that second step, non-specific mucosal responses, is critical (Ishiwata et al. 2002). Further, we suggested that the second step was Stat6-dependent goblet cell-response in mice. Both murine models have implied that CD4+ cells are important for the expulsion. Mice system recently showed the requirement of the IL-13/IL-4 receptor/Stat6 pathway for the adult N. brasiliensis expulsion. We next examined characteristic change in mice goblet cell mucins by lectin histochemistry. Results showed that sialic acid linkage in goblet cell mucin was associated with adult N. brasiliensis expulsion (Ishiwata et al. submitted). Furthermore, the expression of the enzyme, sialyltransferase, was upregulated at the time of worm expulsion or under exogenous IL-13 treatment which induces adult worm expulsion in scid mice. In summary, we suggested a protective mechanism against N. brasiliensis infection in mice as followed : CD4+ cells release IL-13 -> IL-13 binds to IL-4 receptor on goblet cells -> Stat6 activation -> up-regulation of the sialyltransferase expression -> sialic add linkage to mucin -> adult worm expulsion.