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

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 periton...

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Published in:	Infection and Immunity Vol. 78; no. 3; pp. 1364 - 1375
Main Authors:	Johnston, M.J.G, Wang, A, Catarino, M.E.D, Ball, L, Phan, V.C, MacDonald, J.A, McKay, D.M
Format:	Journal Article
Language:	English
Published:	Washington, DC American Society for Microbiology 01-03-2010 American Society for Microbiology (ASM)
Subjects:	Animals Biological and medical sciences Cell Extracts - chemistry Cell Extracts - isolation & purification Cell Extracts - therapeutic use Cell Line Colitis - chemically induced Colitis - drug therapy Colitis - immunology Colitis - pathology Colon - pathology Fundamental and applied biological sciences. Psychology Host Response and Inflammation Humans Hymenolepis diminuta Hymenolepis diminuta - chemistry Hymenolepis diminuta - immunology Immunosuppressive Agents - chemistry Immunosuppressive Agents - isolation & purification Immunosuppressive Agents - therapeutic use Macrophage Activation Macrophages - drug effects Male Mice Mice, Inbred BALB C Microbiology Molecular Weight Vertebrata Mammalia Rat Mouse Rodentia Digestive diseases Intestinal disease Colitis Immunity In vitro Macrophage
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Summary:	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-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) and poly(I:C)-induced TNF-α 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 α-mannosidase failed to inhibit its blockade of LPS-induced TNF-α 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-α 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Editor: J. F. Urban, Jr. M.J.G.J. and A.W. contributed equally to this study.
ISSN:	0019-9567 1098-5522
DOI:	10.1128/IAI.01349-08