Extracts of the Rat Tapeworm, Hymenolepis diminuta, Suppress Macrophage Activation In Vitro and Alleviate Chemically Induced Colitis in Mice

被引:78
作者
Johnston, M. J. G. [1 ]
Wang, A. [1 ]
Catarino, M. E. D. [1 ]
Ball, L. [1 ]
Phan, V. C. [1 ]
MacDonald, J. A. [1 ,2 ]
Mckay, D. M. [1 ]
机构
[1] Univ Calgary, Gastrointestinal Res Grp, Dept Physiol & Pharmacol, Calvin Phoebe & Joan Snyder Inst Infect Immun & I, Calgary, AB T2N 1N4, Canada
[2] Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Smooth Muscle Res Grp, Calgary, AB T2N 1N4, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
EPITHELIAL ION-TRANSPORT; TRICHURIS-SUIS THERAPY; REGULATORY T-CELLS; ALTERNATIVE ACTIVATION; ANTIGENS MODULATE; SECRETED PRODUCT; ASCARIS-SUUM; INFECTION; INFLAMMATION; EXPRESSION;
D O I
10.1128/IAI.01349-08
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-1 beta (IL-1 beta), 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.
引用
收藏
页码:1364 / 1375
页数:12
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