Intestinal nematode infection ameliorates experimental colitis in mice
Intestinal nematode infection ameliorates experimental colitis in mice
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DOI：
10.1128/iai.70.11.5931-5937.2002
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发表时间：
2002-11-01
影响因子：
3.1
通讯作者：
Collins, SM
中科院分区：
文献类型：
--
作者：
Khan, WI;Blennerhasset, PA;Collins, SM
流行病学研究表明，炎症性肠病（IBD）在发达国家很常见，在肠道线虫感染常见的国家很少见。T细胞在许多免疫反应中至关重要，包括与IBD和线虫感染相关的免疫反应。在不同的辅助性T（Th）细胞亚群中，Th1型免疫应答主要与克罗恩病相关，而许多线虫感染产生强烈的Th2应答。Th1和Th2细胞之间的相互交叉调节表明，线虫产生的Th2应答可以预防或减少Th1介导的疾病的影响。在本研究中，我们研究了极化的免疫反应对Th2型，使用肠道线虫感染，随后的实验性结肠炎的影响。用肠道线虫旋毛虫感染小鼠，并使其恢复，然后用二硝基苯磺酸诱导结肠炎。结肠炎后处死小鼠，以评估结肠损伤宏观，组织学，髓过氧化物酶（MPO）活性和Th细胞因子。先前的线虫感染降低了结肠炎的严重程度，无论是宏观和组织学上的死亡率降低，并与下调MPO活性，结肠组织中的Th1型细胞因子表达，并出现了Th2型免疫应答。这些结果表明线虫感染在Th1细胞驱动的炎症中具有保护作用，并提示考虑基于免疫分散的IBD新治疗策略。
Epidemiological studies suggest that inflammatory bowel disease (IBD) is common in developed countries and rare in countries where intestinal nematode infections are common. T cells are critical in many immune responses, including those associated with IBD and nematode infection. Among the distinct T helper (Th) cell subsets, Th1-type immune response is predominantly associated with Crohn's disease, while many nematode infections generate a strong Th2 response. The reciprocal cross regulation between Th1 and Th2 cells suggests that generation of a Th2 response by nematodes could prevent or reduce the effects of Th1-mediated diseases. In the present study, we investigated the effect of polarizing the immune response toward the Th2 type, using intestinal nematode infection, on subsequent experimental colitis. Mice were infected with the intestinal nematode Trichinella spiralis and allowed to recover before colitis was induced with dinitrobenzene sulfonic acid. The mice were sacrificed postcolitis to assess colonic damage macroscopically, histologically, and by myeloperoxidase (MPO) activity and Th cytokines. Prior nematode infection reduced the severity of colitis both macroscopically and histologically together with a decreased mortality and was correlated with a down-, regulation of MPO activity, Th1-type cytokine expression in colonic tissue, and emergence of a Th2-type immune response. These results indicate a protective role of nematode infection in Th1 cell-driven inflammation and prompt consideration of a novel therapeutic strategy in IBD based on immunological distraction.