Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice

Ruyssers, Nathalie E.; Winter, Benedicte Y. De; Man, Joris G. De; Loukas, Alex; Pearson, Mark S.; Weinstock, Joel V.; Bossche, Rita M. Van den; Martinet, Wim; Pelckmans, Paul; Moreels, Tom G.

doi:10.1002/ibd.20787

Cited by 155 publications

(164 citation statements)

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“…The data presented here are the aggregate of experiments using five different preparations of H. diminuta to generate five different HdHMW preparations. Based on the antigenic complexity of H. diminuta (38), crude homogenates from entire adult worms were compared to that from worms lacking the anterior 2 cm, which comprises the scolex and neck region.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…Indeed, a number of parasite-derived products have shown some protective ability in immunopathology models [16,17]. Products of Ancylostoma caninum [43,44] . We report below that co-administration of HES with sensitising allergen inhibits both innate and adaptive arms of the immune response, including eosinophilia, type 2 innate response markers, antibody generation and effector T-cell reactivity.…”

mentioning

confidence: 99%

Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminthHeligmosomoides polygyrus

McSorley

O'Gorman

Blair³

et al. 2012

Eur J Immunol

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Allergic asthma is less prevalent in countries with parasitic helminth infections, and mice infected with parasites such as Heligmosomoides polygyrus are protected from allergic airway inflammation. To establish whether suppression of allergy could be mediated by soluble products of this helminth, we tested H. polygyrus excretory-secretory (HES) material for its ability to impair allergic inflammation. When HES was added to sensitising doses of ovalbumin, the subsequent allergic airway response was suppressed, with ablated cell infiltration, a lower ratio of effector (CD4 + CD25 + Foxp3 − ) to regulatory (CD4 + Foxp3 + ) T (Treg) cells, and reduced Th1, Th2 and Th17 cytokine production. HES exposure reduced IL-5 responses and eosinophilia, abolished IgE production and inhibited the type 2 innate molecules arginase-1 and RELM-α (resistin-like molecule-α). Although HES contains a TGF-β-like activity, similar effects in modulating allergy were not observed when administering mammalian TGF-β alone. HES also protected previously sensitised mice, suppressing recruitment of eosinophils to the airways when given at challenge, but no change in Th or Treg cell populations was apparent. Because heat-treatment of HES did not impair suppression at sensitisation, but compromised its ability to suppress at challenge, we propose that HES contains distinct heat-stable and heat-labile immunomodulatory molecules, which modulate pro-allergic adaptive and innate cell populations.Keywords: Allergy r Eosinophils r IgE r Infection r Macrophages IntroductionAllergic asthma has dramatically increased in prevalence in developing countries, exceeding 5% of the Western European and North American populations [1]. This contrasts with much lower asthma incidence in tropical countries that have significant levels of parasite infections, and these observations have stimulated research into the effects of parasitic organisms on human allergy [2][3][4]. From these studies, it has emerged that allergic diseases are least common in parts of the world with high helminth endemicity, and that within endemic populations the prevalence of atopy is significantly lower in individuals with chronic worm infections [5][6][7][8][9][10].Correspondence: Dr. Rick M. Maizels e-mail: rick.maizels@ed.ac.ukWhile a causal link between human helminth infections and reduced allergy has yet to be proven [2], chemotherapeutic clearance of intestinal helminths can result in accentuated atopic responsiveness [11][12][13] and helminth infection blocks overt allergy in a number of animal models [14][15][16][17]. The degree to which helminths may influence allergy, however, is clearly variable between different parasite species [18], and is probably dependent upon the duration and intensity of infection [2,19], each factors that need to be taken into account in assessing this interaction.The concept that helminths may act in a beneficial way for therapy of immunological disorders is one that has been gaining * These author contributed equally to this work. Eur. J. Immunol. 20...

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“…colonic tissue and mesenteric lymph nodes. 15 In addition, T. suis egg therapy has already successfully been tried in CD patients. 16 Trichinella spiralis infection brought a similar protective effect in DNBS--induced colitis mice, which was associated with an IFN-γ and IL-12 decrease.…”

Section: Proteins From Anisakis Simplex L3 Can Change the Cytokine Prmentioning

confidence: 99%

Preventive and Therapeutic Effects of <italic>Anisakis simplex</italic> Larval Protein in a Mouse Model of Crohn’S Disease

Cha

Ock

2013

KMJ

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Objectives: Some helminths have been known to have a treatment effect in inflammatory bowel diseases, including Crohn's disease (CD); however, live parasite therapy can cause unwanted side effects. To develop a safe therapeutic, we investigated the preventive or therapeutic potential of proteins from the third stage larva of A. simplex in a mouse model. We also analyzed the cytokine profile from splenic and mesenteric lymph node lymphocytes to elucidate the underlying immunological mechanism. Methods: CD was induced in mice with DSS, and the effect of an A. simplex larval protein on CD was assessed. A change in body weight and DAI (disease activity index) were observed in mice. The expression levels of cytokines from mesenteric lymph nodes (MLN) compared to splenic lymphocytes were measured with ELISA. Results: Peritoneal administration of preventive and therapeutic A. simplex larval proteins attenuated DSS-induced CD by a reduction of the DAI and weight loss. A shortening of colon length was more definitely observed in the therapeutic group than in the preventive group. The cytokine expression levels were more obvious in lymphocytes from mesenteric lymph nodes than from splenic lymphocytes. Conclusions: Taken together, these results suggest that A. simplex proteins can change cytokine profiles and may have a preventive effect in DSS-induced CD mice.

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Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice

Cited by 155 publications

References 51 publications

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

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

Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminthHeligmosomoides polygyrus

Preventive and Therapeutic Effects of <italic>Anisakis simplex</italic> Larval Protein in a Mouse Model of Crohn’S Disease

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Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice

Cited by 155 publications

References 51 publications

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

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

Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminthHeligmosomoides polygyrus

Preventive and Therapeutic Effects of &lt;italic&gt;Anisakis simplex&lt;/italic&gt; Larval Protein in a Mouse Model of Crohn’S Disease

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Preventive and Therapeutic Effects of <italic>Anisakis simplex</italic> Larval Protein in a Mouse Model of Crohn’S Disease