Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute of Infection, Immunity, and Inflammation, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 1N4, Canada.
Infect Immun. 2010 Mar;78(3):1364-75. doi: 10.1128/IAI.01349-08. Epub 2009 Dec 22.
Analysis of parasite-host interactions can reveal the intricacies of immunity and identify ways to modulate immunopathological reactions. We assessed the ability of a phosphate-buffered saline-soluble extract of adult Hymenolepis diminuta to suppress macrophage (human THP-1 cell line, murine peritoneal macrophages) activity in vitro and the impact of treating mice with this extract on colitis induced by dinitrobenzene sulfonic acid (DNBS). A high-molecular-mass fraction of adult H. diminuta (HdHMW) or excretory/secretory products reduced macrophage activation: lipopolysaccharide (LPS)-induced interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) and poly(I:C)-induced TNF-alpha and IL-6 were suppressed by HdHMW. The active component in the HdHMW extract was minimally sensitive to boiling and trypsin digestion, whereas the use of sodium metaperiodate, as a general deglycosylation strategy, indicated that the immunosuppressive effect of HdHMW was at least partially dependent on a glycan: treating the HdHMW with neuraminidase and alpha-mannosidase failed to inhibit its blockade of LPS-induced TNF-alpha production by THP-1 macrophages. Mice treated with DNBS developed colitis, as typified by wasting, shortening of the colon, macroscopic and microscopic tissue damage, and an inflammatory infiltrate. Mice cotreated with HdHMW (three intraperitoneal injections) displayed significantly less inflammatory disease, and this was accompanied by reduced TNF-alpha production and increased IL-10 and IL-4 production by mitogen-stimulated spleen cells. However, cotreatment of mice with neutralizing anti-IL-10 antibodies had only a minor impact on the anticolitic effect of the HdHMW. We speculate that purification of the immunosuppressive factor(s) from H. diminuta has the potential to lead to the development of novel immunomodulatory drugs to treat inflammatory disease.
寄生虫-宿主相互作用的分析可以揭示免疫的复杂性，并确定调节免疫病理反应的方法。我们评估了一种来自微小膜壳绦虫成虫的磷酸盐缓冲盐水可溶提取物在体外抑制巨噬细胞（人 THP-1 细胞系，鼠腹腔巨噬细胞）活性的能力，以及用该提取物治疗二硝基苯磺酸（DNBS）诱导结肠炎的小鼠的影响。成年微小膜壳绦虫的高分子质量部分（HdHMW）或排泄/分泌产物降低了巨噬细胞的激活：脂多糖（LPS）诱导的白细胞介素-1β（IL-1β）、IL-6 和肿瘤坏死因子-α（TNF-α）以及聚 I:C 诱导的 TNF-α和 IL-6 被 HdHMW 抑制。HdHMW 提取物中的活性成分对煮沸和胰蛋白酶消化的敏感性较低，而使用高碘酸钠作为一般的去糖基化策略表明，HdHMW 的免疫抑制作用至少部分依赖于糖：用神经氨酸酶和α-甘露糖苷酶处理 HdHMW 未能抑制其阻断 LPS 诱导的 THP-1 巨噬细胞产生 TNF-α。用 DNBS 处理的小鼠发生结肠炎，表现为消瘦、结肠缩短、组织损伤的宏观和微观表现以及炎症浸润。用 HdHMW（三次腹腔注射）共同处理的小鼠显示出炎症性疾病明显减少，这伴随着刺激脾细胞产生的 TNF-α减少和 IL-10 和 IL-4 增加。然而，用中和抗 IL-10 抗体共同处理小鼠对 HdHMW 的抗结肠炎作用只有轻微影响。我们推测，从微小膜壳绦虫中纯化免疫抑制因子（s）有可能开发出新型免疫调节剂药物来治疗炎症性疾病。
