Helminth infection enhances disease in a murine TH2 model of colitis
Helminth infection enhances disease in a murine TH2 model of colitis
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DOI：
10.1053/j.gastro.2007.01.038
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发表时间：
2007-04-01
期刊：
影响因子：
29.4
通讯作者：
McKay, Derek M.
中科院分区：
文献类型：
--
作者：
Hunter, Meaghan M.;Wang, Arthur;McKay, Derek M.
背景和目的：动物和人类研究中有令人信服的证据表明，寄生蠕虫感染可以减轻结肠炎的组织病理学和症状。这里评估了大鼠绦虫 Hymenolepis diminuta 影响恶唑酮诱导的结肠炎（TH2 模型）病程的能力。方法：小鼠感染 H diminuta，8 天后接受恶唑酮（3 mg，溶于 50% EtOH，直肠内注射）。尸检时（恶唑酮后 3 或 7 天），通过宏观临床评分、组织学损伤评分、髓过氧化物酶和嗜酸性粒细胞过氧化物酶活性以及细胞因子合成来评估疾病严重程度。结果：根据所有肠道功能标志物的评估，H diminuta 感染导致恶唑酮诱发的结肠炎显着恶化。事实上，虽然接受恶唑酮的小鼠在治疗后 3-4 天才开始恢复，但联合治疗组的情况却继续恶化。与恶唑酮给药无关，蠕虫感染可增强体外刺激免疫细胞产生的 IL-4、IL-5、IL-10 和 IL-13，并引起联合治疗小鼠结肠嗜酸性粒细胞过氧化物酶的增加。最后，虽然通过给予中和性 NK1.1 抗体敲除自然杀伤 (NK) 和 NK-T 细胞可减少恶唑酮和恶唑酮 + H diminuta 治疗动物的炎症，但后一组小鼠仍表现出明显的结肠炎。结论：我们已经证明 H diminuta 感染对其他结肠炎模型有益。目前的数据是对这样一种立场的警告，即在不仔细分析该病症的免疫学基础的情况下，一般可以将寄生蠕虫视为异质性炎症性疾病的治疗方法。
Background & Aims: There is convincing evidence from animal and human studies that infection with parasitic helminths can alleviate the histopathology and symptoms of colitis. Here the ability of the rat tapeworm Hymenolepis diminuta to affect the course of oxazolone-induced colitis (a TH2 model) was assessed. Methods: Mice were infected with H diminuta and 8 days later they received oxazolone (3 mg in 50% EtOH, intrarectal). On autopsy (3 or 7 days postoxazolone), disease severity was assessed by macroscopic clinical scores, histologic damage scores, myeloperoxidase and eosinophil peroxidase activity, and cytokine synthesis. Results: As gauged by all markers of gut function, infection with H diminuta caused a significant exacerbation of oxazolone-induced colitis. Indeed, while mice receiving oxazolone only began to recover similar to 3-4 days posttreatment, the cotreated group continued to deteriorate. Helminth infection, independent of oxazolone administration, enhanced IL-4, IL-5, IL-10, and IL-13 production from in vitro stimulated immune cells and evoked increases in colonic eosinophil peroxidase of cotreated mice. Finally, while knockout of natural killer (NK) and NK-T cells by administration of a neutralizing NK1.1 antibody reduced the inflammation in oxazolone and oxazolone + H diminuta-treated animals, mice in the latter group still displayed significant colitis. Conclusions: We have shown that H diminuta infection is beneficial in other models of colitis. The current data is presented as a caveat to the position that parasitic helminths in general can be considered as a therapy for heterogeneous inflammatory disorders without careful analysis of the immunologic basis of the condition.