Enteric nematodes induce stereotypic STAT6-dependent alterations in intestinal epithelial cell function
Enteric nematodes induce stereotypic STAT6-dependent alterations in intestinal epithelial cell function
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DOI：
10.4049/jimmunol.172.9.5616
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Shea-Donohue, T
中科院分区：
文献类型：
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作者：
Madden, KB;Yeung, KA;Shea-Donohue, T
胃肠道线虫感染对宿主的免疫和生理反应都有深远影响。我们之前已表明，Th2细胞因子白细胞介素 - 4（IL - 4）和白细胞介素 - 13（IL - 13）诱导肠道上皮细胞通透性、吸收和分泌发生依赖于STAT6的变化，这些变化与多形螺旋线虫二次感染时观察到的情况相似。在当前的研究中，我们探讨了线虫对上皮细胞功能的影响是否：1）具有普遍性；2）依赖于STAT6；3）是由对上皮细胞本身的直接影响导致，还是由对肠神经的影响所介导。我们的研究结果表明，用三种不同的胃肠道线虫（多形螺旋线虫、巴西日圆线虫和旋毛虫）感染BALB/c小鼠会改变肠道上皮细胞功能，表现为电阻降低、葡萄糖吸收减少以及对5 - 羟色胺和乙酰胆碱这两种黏膜下反射通路中的关键介质的分泌反应减弱。这些改变的反应依赖于STAT6，是直接影响以及通过肠神经介导的间接影响共同作用的结果。
Infection with gastrointestinal nematodes exerts profound effects on both the immune and physiological responses of the host. We showed previously that the Th2 cytokines, IL-4 and IL-13, induce STAT6-dependent changes in intestinal epithelial cell permeability, absorption, and secretion that are similar to those observed in a secondary infection with Heligmosomoides polygyrus. In the current study we investigated whether nematode-induced effects on epithelial cell function were 1) generic, 2) dependent upon STAT6, and 3) attributable to direct effects on the epithelial cells themselves or mediated by effects on enteric nerves. Our results demonstrate that infection of BALB/c mice with three different gastrointestinal nematodes (H. polygyrus, Nippostrongylus brasiliensis, and Trichinella spiralis) alters intestinal epithelial cell function by decreasing resistance, glucose absorption, and secretory responses to 5-hydroxytryptamine and acetylcholine, two critical mediators in the submucosal reflex pathway. These modified responses are dependent on STAT6 and are the result of both direct effects and indirect effects mediated through enteric nerves.