Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta

Wang, A.; McKay, Derek M.

doi:10.1017/s0031182004006985

Cited by 26 publications

(34 citation statements)

References 27 publications

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“…In this and other studies (Isaak 1983;Palmas et al 1984Palmas et al , 1986Gabriele et al 1986;Shinoda and Asano 1989;Mangoud et al 1991;Claveria et al 2005;Wang and McKay 2005), only small alterations were recorded in the rat adrenal glands during experimental hymenolepiasis. The changes take place essentially in zona fascicularis (Palmas et al 1984, present study), the adaptive reaction of which is the mobilization of cytoplasmatic lipids in connection with the steroid hormone synthesis.…”

Section: Stanis³asupporting

confidence: 51%

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Experimental hymenolepiasis of rats: preliminary data on histopathological changes of visceral organs

Movsesyan

Jivanyan

Chubaryan

et al. 2008

Acta Parasitologica

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Pathomorphological changes of intestine, liver, spleen and adrenals of rats experimentally infected with Hymenolepis diminuta are described 24 days post infection. Major structural alterations in intestinal wall include lesions of the mucosa, fusions of villi, damage of the epithelial layer and its replacement by flattened cells with pycnotic nuclei. In addition, tunica muscularis and tunica submucosa become thicker and there are numerous lymphocytes among enterocytes. At moderate infections, the changes in the spleen indicate activation of the lymphopoiesis and enhanced protective functions while, in heavily infected rats, the B zone of the spleen showed signs of emaciation. Liver histology of infected rats showed dilatation of sinusoids and the presence of destructive alterations in the parenchyma, necrotic cells and cells with pycnotic nuclei; in heavily infected animals, the necrotic cells were grouped in foci. In adrenal glands, alterations concern mostly zona fascicularis, which is interpreted as mobilization of cytoplasmic lipid inclusions in order to increase the intensity of the steroid hormone synthesis. The degree and character of histopathological changes depended on the intensity of infection.

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Section: Stanis³asupporting

confidence: 51%

“…As demonstrated by Wang and McKay (2005), H. diminuta could block the activation of the T-cell proliferation by interleukin-4 inhibition. The T-cell inhibition was also observed in hymenolepiasis caused by R. nana (Shinoda and Asano 1989).…”

Section: Introductionmentioning

confidence: 93%

Experimental hymenolepiasis of rats: preliminary data on histopathological changes of visceral organs

Movsesyan

Jivanyan

Chubaryan

et al. 2008

Acta Parasitologica

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“…Using DNBS to evoke what is considered a Th1-driven colitis (24), the present study shows that H. diminuta infection in a prophylactic regimen almost abolished the colitis, as assessed by clinical parameters, histological assessment, and biochemical markers (i.e., MPO). One interpretation of the data is that H. diminuta ameliorates colitis via the release of a particular factor, and indeed, like other parasitic helminths (25), H. diminuta Ag can block mitogen-driven T cell responses in vitro (26). However, in the nonpermissive murine system, the helminth never establishes or attains a significant biomass (15).…”

Section: Discussionmentioning

confidence: 99%

Neutralizing Anti-IL-10 Antibody Blocks the Protective Effect of Tapeworm Infection in a Murine Model of Chemically Induced Colitis

Hunter

Wang

Hirota

et al. 2005

The Journal of Immunology

151

212

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There is increasing evidence that parasitic helminth infection has the ability to ameliorate other disease conditions. In this study the ability of the rat tapeworm, Hymenolepis diminuta, to modulate dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice is assessed. Mice receiving DNBS (3 mg intrarectally) developed colitis by 72 h after treatment. Mice infected 8 days before DNBS with five H. diminuta larvae were significantly protected from the colitis, as gauged by reduced clinical disease, histological damage scores, and myeloperoxidase levels. This anticolitic effect was dependent on a viable infection and helminth rejection, because no benefit was observed in mice given killed larvae or in infected STAT6 knockout mice or rats, neither of which eliminate H. diminuta. The anticolitic effect of H. diminuta was associated with increased colonic IL-10 mRNA and stimulated splenocytes from H. diminuta- plus DNBS-treated mice produced more IL-10 than splenocytes from DNBS-only treated mice. Coadministration of an anti-IL-10 Ab blocked the anticolitic effect of prophylactic H. diminuta infection. Also, mice infected 48 h after DNBS treatment showed an enhanced recovery response. Finally, using a model of OVA hypersensitivity, we found no evidence of concomitant H. diminuta infection enhancing enteric responsiveness to subsequent ex vivo OVA challenge. The data show that a viable infection of H. diminuta in a nonpermissive system exerts a profound anticolitic effect (both prophylactically and as a treatment) that is mediated at least in part via IL-10 and does not predispose to enhanced sensitivity to bystander proteins.

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“…Adult H. diminuta worms were flushed from the small intestine of rats and rinsed (four times) in normal saline at room temperature (45). Then, 20-g (wet weight) portions of H. diminuta were transferred into 20-ml portions of sterile PBS and homogenized on ice at maximum speed for 5 min by using a Polytron PT1200 homogenizer (Kinematica, Inc., New York, NY).…”

Section: Methodsmentioning

confidence: 99%

“…We previously demonstrated that a crude extract of H. diminuta significantly reduced proliferation and cytokine production by human and murine T cells (45). Reasoning that the immunosuppressive effect need not be restricted to T cells, the present study assessed the ability of a high-molecular-mass fraction from adult H. diminuta (HdHMW) and excreted and/or secreted products (HdES) to block macrophage activa-tion, as assessed mainly by tumor necrosis factor alpha (TNF-␣) production.…”

mentioning

confidence: 99%

Extracts of the Rat Tapeworm,Hymenolepis diminuta, Suppress Macrophage ActivationIn Vitroand Alleviate Chemically Induced Colitis in Mice

et al. 2010

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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.

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Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta

Cited by 26 publications

References 27 publications

Experimental hymenolepiasis of rats: preliminary data on histopathological changes of visceral organs

Experimental hymenolepiasis of rats: preliminary data on histopathological changes of visceral organs

Neutralizing Anti-IL-10 Antibody Blocks the Protective Effect of Tapeworm Infection in a Murine Model of Chemically Induced Colitis

Extracts of the Rat Tapeworm,Hymenolepis diminuta, Suppress Macrophage ActivationIn Vitroand Alleviate Chemically Induced Colitis in Mice

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