Sutton Thomas L, Zhao Aiping, Madden Kathleen B, Elfrey Justin E, Tuft Blaine A, Sullivan Carolyn A, Urban Joseph F, Shea-Donohue Terez
Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC 20307, USA.
Infect Immun. 2008 Oct;76(10):4772-82. doi: 10.1128/IAI.00744-07. Epub 2008 Jul 21.
Recent studies showed that enteric helminth infection improved symptoms in patients with inflammatory bowel disease as well as in experimental models of colitis. The aim of this study was to determine the mechanism of the protective effect of helminth infection on colitis-induced changes in immune and epithelial cell function. BALB/c mice received an oral infection of Heligmosomoides polygyrus third-stage larvae, were given intrarectal saline or trinitrobenzene sulfonic acid (TNBS) on day 10 postinfection, and were studied 4 days later. Separate groups of mice received intrarectal saline or TNBS on day 10 and were studied on day 14. Muscle-free colonic mucosae were mounted in Ussing chambers to measure mucosal permeability and secretion. Expression of cytokines was assessed by quantitative real-time PCR, and mast cells were visualized by immunohistochemistry. TNBS-induced colitis induced mucosal damage, upregulated Th1 cytokines, and depressed secretory responses. Heligmosomoides polygyrus elevated Th2 cytokine expression, increased mast cell infiltration and mucosal resistance, and also reduced some secretory responses. Prior H. polygyrus infection prevented TNBS-induced upregulation of Th1 cytokines and normalized secretory responses to specific agonists. TNBS-induced colitis did not alter H. polygyrus-induced mast cell infiltration or upregulation of Th2 cytokine expression. The results indicate that the protective mechanism of enteric nematode infection against TNBS-induced colitis involves prevention of Th1 cytokine expression and improved colonic function by a mechanism that may involve mast cell-mediated protection of neural control of secretory function. Similar response patterns could account for the clinical improvement seen in inflammatory bowel disease with helminthic therapy.
近期研究表明，肠道蠕虫感染可改善炎症性肠病患者以及结肠炎实验模型的症状。本研究的目的是确定蠕虫感染对结肠炎诱导的免疫和上皮细胞功能变化产生保护作用的机制。BALB/c小鼠口服感染多形螺旋线虫第三期幼虫，在感染后第10天经直肠给予生理盐水或三硝基苯磺酸（TNBS），并于4天后进行研究。另一组小鼠在第10天经直肠给予生理盐水或TNBS，并于第14天进行研究。将无肌肉的结肠黏膜置于尤斯灌流小室中以测量黏膜通透性和分泌功能。通过定量实时PCR评估细胞因子的表达，并通过免疫组织化学观察肥大细胞。TNBS诱导的结肠炎导致黏膜损伤，上调Th1细胞因子，并抑制分泌反应。多形螺旋线虫可提高Th2细胞因子的表达，增加肥大细胞浸润和黏膜抵抗力，还可降低一些分泌反应。预先感染多形螺旋线虫可防止TNBS诱导的Th1细胞因子上调，并使对特定激动剂的分泌反应恢复正常。TNBS诱导的结肠炎并未改变多形螺旋线虫诱导的肥大细胞浸润或Th2细胞因子表达的上调。结果表明，肠道线虫感染对TNBS诱导的结肠炎的保护机制包括预防Th1细胞因子表达，并通过一种可能涉及肥大细胞介导的对分泌功能神经控制的保护机制改善结肠功能。类似的反应模式可以解释蠕虫疗法在炎症性肠病中所见的临床改善情况。
