Gastrointestinal Research Group and Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Joan, and Phoebe Snyder Institute for Chronic Disease, Cumming School of Medicine, University of Calgary , Calgary, Alberta , Canada.
Am J Physiol Gastrointest Liver Physiol. 2018 Apr 1;314(4):G461-G470. doi: 10.1152/ajpgi.00295.2017. Epub 2018 Jan 4.
Infection with helminth parasites reduces the severity of concomitant inflammatory disease in adult mice. There is an alarming increase of inflammatory bowel disease (IBD) in children. It is important to determine whether helminth therapy would be of value in pediatric IBD and whether triggering immunological memory to the worm would be anticolitic. Three-week-old (young) and eight-week-old (adult) Balb/c mice were infected with H. diminuta, and infectivity and T helper 2 (Th2) immunity were assessed. Other mice received H. diminuta with or without a crude worm extract ( HdE) 28-42 days postinfection (dpi) with or without dinitrobenzene sulphonic acid [DNBS, 1.5 mg (young) or 3 mg (adults), ir], and colitis was assessed 72 h later. Infected young mice developed Th2 immunity and expelled H. diminuta; expulsion was delayed by ~2 days compared with adult mice. Colitis, as gauged by macroscopic disease and histopathology scores, was less severe in young mice infected 10 days, but not 8 days, before DNBS. Protection against DNBS-induced colitis was accompanied by an increased capacity to make interleukin (IL)-4 and IL-10. Mice infected with H. diminuta were not protected from DNBS-colitis when challenged 28 days later; however, injection of these mice with HdE coincident with DNBS resulted in less disease and increased splenic IL-4 and IL-10. Using a boost (500 μg HdE, 28 dpi) and repeat HdE (100 μg, 42 dpi) regimen with infected mice suppressed DNBS-colitis, as did adoptive transfer of splenic CD4 T cells from infected mice with low-dose HdE challenge. Should these data translate to IBD, then helminth therapy could be of value in pediatric-onset IBD, and defining the antigen(s) that elicit antihelminth immunological memory could serve as an anticolitic approach in previously infected individuals. NEW & NOTEWORTHY This study demonstrates that juvenile mice are protected from colitis by infection with the tapeworm Hymenolepis diminuta and that using worm antigen to trigger an immunological memory response in previously infected mice can be used to limit the severity of colitis.
寄生虫感染会减轻成年小鼠伴发炎症性疾病的严重程度。儿童炎症性肠病(IBD)的发病率正在惊人地上升。因此,有必要确定在儿科 IBD 中,是否使用抗蠕虫疗法会有价值,以及触发对蠕虫的免疫记忆是否具有抗结肠炎作用。将 3 周龄(幼龄)和 8 周龄(成年)的 Balb/c 小鼠感染细粒棘球蚴(H. diminuta),并评估其感染性和 T 辅助 2(Th2)免疫。其他小鼠在感染后 28-42 天(dpi)接受细粒棘球蚴和/或粗虫提取物(HdE)治疗,同时接受二硝基苯磺酸[DNBS,幼龄鼠 1.5 mg(幼龄)或 3 mg(成年),ir],72 小时后评估结肠炎。感染幼龄鼠产生 Th2 免疫并排出 H. diminuta;与成年鼠相比,排出时间延迟了约 2 天。幼龄鼠在感染后 10 天而不是 8 天接受 DNBS 前处理时,结肠炎的宏观疾病和组织病理学评分较轻。对 DNBS 诱导的结肠炎的保护作用伴随着白细胞介素(IL)-4 和 IL-10 产生能力的增加。当 28 天后再次用 H. diminuta 感染时,感染的小鼠未受到 DNBS 结肠炎的保护;然而,当这些小鼠在接受 DNBS 的同时注射 HdE 时,疾病减轻,脾内 IL-4 和 IL-10 增加。使用感染小鼠的增强(500 μg HdE,28 dpi)和重复 HdE(100 μg,42 dpi)方案抑制了 DNBS 结肠炎,用低剂量 HdE 挑战感染小鼠的脾 CD4 T 细胞过继转移也抑制了 DNBS 结肠炎。如果这些数据可以转化为 IBD,那么抗蠕虫疗法可能对儿科 IBD 有价值,并且确定引发抗蠕虫免疫记忆的抗原可以作为先前感染个体的抗结肠炎方法。本研究表明,幼龄小鼠感染细粒棘球蚴可预防结肠炎,并且使用蠕虫抗原在先前感染的小鼠中触发免疫记忆反应可用于限制结肠炎的严重程度。