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

Johnston, Michael J.; Wang, A.; Catarino, Michael; Ball, LuAnn; Phan, Van-Duc; MacDonald, Justin A.; McKay, Derek M.

doi:10.1128/iai.01349-08

Cited by 90 publications

(100 citation statements)

References 49 publications

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“…Treatment with HdAg could ameliorate colitis via a variety of mechanisms (1,21,22). Antigens from the flatworms S. mansoni and Taenia crassiceps can mobilize myeloid-derived suppressor cells (MDSCs) (27,28).…”

Section: Resultsmentioning

confidence: 99%

“…The protein concentration in the HdAg preparations was determined by the Bradford assay (Bradford reagent; Sigma-Aldrich, St. Louis MO), and aliquots were stored at Ϫ80°C. Three separate HdAg preparations were used in this investigation, and each suppressed LPS-induced tumor necrosis factor alpha (TNF-␣) production from the THP-1 monocytic cell line by at least 40% (21).…”

Section: Ethicsmentioning

confidence: 99%

“…Daily intraperitoneal (i.p.) doses (1 mg) of a high-molecularweight (MW) crude extract of adult H. diminuta over the 3 days of DNBS treatment significantly reduced the severity of inflammation in the colon (21 …”

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confidence: 99%

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Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 ⁺ Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis

et al. 2016

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Awareness of the immunological underpinnings of host-parasite interactions may reveal immune signaling pathways that could be used to treat inflammatory disease in humans. Previously we showed that infection with the rat tapeworm, Hymenolepis diminuta, used as a model helminth, or systemic delivery of worm antigen (HdAg) significantly reduced the severity of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice. Extending these analyses, intraperitoneal injection of HdAg dosedependently suppressed dextran sodium sulfate (DSS)-induced colitis, and this was paralleled by reduced gamma interferon (IFN-␥), interleukin-17 (IL-17), and tumor necrosis factor alpha (TNF-␣) production and increased IL-10 production from mitogen-activated splenocytes. Until relatively recently, analysis of the host response to infection with helminth parasites focused almost invariably on TH2 immunity; however, it has emerged that helminth parasites trigger a complex regulatory network in their mammalian hosts that is characterized by cytokines (e.g., interleukin-10 [IL-10] and transforming growth factor ␤ [TGF-␤]) and cellular components (e.g., regulatory macrophages and T cells) (1). Indeed, the development of an immunoregulatory environment likely contributes to the chronicity of helminth infection and asymptomatic disease. Moreover, individuals infected with a variety of species of helminths can be protected from concomitant disease as demonstrated in animal models of multiple sclerosis (2-4), joint (5-7) and gut (8-10) inflammation, and allergy (11, 12). In addition, treatment with somatic extracts or secreted products can significantly attenuate disease severity in models of inflammatory diseases (13-15), raising the possibility that isolation and purification of helminth-derived molecules could result in new anti-inflammatory drugs.The inverse relationship between the geographical distribution of inflammatory bowel disease (IBD) (i.e., Crohn's disease and ulcerative colitis) and areas of endemic helminth infection suggests that infection with helminth parasites may protect against IBD (16). Testing this hypothesis, infections with Trichinella spiralis, Schistosoma mansoni, and Heligmosomoides polygyrus were shown to inhibit inflammation in dinitrobenzene sulfonic acid (DNBS)-and dextran-sodium sulfate (DSS)-induced colitis and piroxicam-treated IL-10 Ϫ/Ϫ mice, respectively (8, 9, 17)-all established mouse models of colitis that share some similarities to human IBD. Similarly, and as an alternative to viable infection, systemic administration of helminth-derived antigens can ameliorate colitis in animal models. As examples, the excretory/secretory (E/S) products from adult T. spiralis reduced DSS-induced colitis (18) and S. mansoni egg antigens ameliorated immunemediated colitis (19): in both instances, suppression of TH1 and TH17 cytokines correlated with the beneficial anticolitic effect. While encouraging, the precise mechanism of action of any helminth-derived extract or molecule to block colitis or other inflammatory dis...

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Section: Resultsmentioning

confidence: 99%

Section: Ethicsmentioning

confidence: 99%

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Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 ⁺ Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis

et al. 2016

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“…delivery of either DNBS or oxazolone (pilot studies with 3 3 10 6 /ml splenic CD19 + cells produced inconsistent data) or when regular drinking water was replaced with 5% w/v DSS-drinking water. In addition, B cells from naive mice were treated in vitro for 48 h with either murine recombinant IL-4 plus IL-13 (both 10 ng/ml; Cedarlane Laboratories, Burlington, ON, Canada; referred to as BcIL-4/13) or 1 mg/ml of a PBS-soluble crude Ag extract of whole adult H. diminuta (referred to as HdAg) (26). The cells were rinsed extensively with PBS and used in transfer experiments.…”

Section: B Cell Isolation and Experimental Designmentioning

confidence: 99%

Splenic B Cells fromHymenolepis diminuta–Infected Mice Ameliorate Colitis Independent of T Cells and via Cooperation with Macrophages

Reyes

Wang

Fernando

et al. 2015

The Journal of Immunology

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Helminth parasites provoke multicellular immune responses in their hosts that can suppress concomitant disease. The gut lumen-dwelling tapeworm Hymenolepis diminuta, unlike other parasites assessed as helminth therapy, causes no host tissue damage while potently suppressing murine colitis. With the goal of harnessing the immunomodulatory capacity of infection with H. diminuta, we assessed the putative generation of anti-colitic regulatory B cells following H. diminuta infection. Splenic CD19+ B cells isolated from mice infected 7 [HdBc(7d)] and 14 d (but not 3 d) previously with H. diminuta and transferred to naive mice significantly reduced the severity of dinitrobenzene sulfonic acid (DNBS)-, oxazolone-, and dextran-sodium sulfate–induced colitis. Mechanistic studies with the DNBS model, revealed the anti-colitic HdBc(7d) was within the follicular B cell population and its phenotype was not dependent on IL-4 or IL-10. The HdBc(7d) were not characterized by increased expression of CD1d, CD5, CD23, or IL-10 production, but did spontaneously, and upon LPS plus anti-CD40 stimulation, produce more TGF-β than CD19+ B cells from controls. DNBS-induced colitis in RAG1−/− mice was inhibited by administration of HdBc(7d), indicating a lack of a requirement for T and B cells in the recipient; however, depletion of macrophages in recipient mice abrogated the anti-colitic effect of HdBc(7d). Thus, in response to H. diminuta, a putatively unique splenic CD19+ B cell with a functional immunoregulatory program is generated that promotes the suppression of colitis dominated by TH1, TH2, or TH1-plus-TH2 events, and may do so via the synthesis of TGF-β and the generation of, or cooperation with, a regulatory macrophage.

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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], Hymenolepis diminuta [45], Schistosoma mansoni [44] and Trichinella spiralis [46] all contain immunomodulators which can suppress pathology in mouse models of colitis, while somatic constituents of Ascaris suum can inhibit allergic inflammation [47,48], as can secretions of Nippostrongylus brasiliensis [49]. Physiologically, active immunomodulators are most likely to be secreted from live parasites into their host environment [50], and in this report we focus on the H. polygyrus excretory-secretory (HES) products as potential modulators of airway allergy in a mouse model.…”

Section: Introductionmentioning

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

Cited by 90 publications

References 49 publications

Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 ⁺ Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis

Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 ⁺ Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis

Splenic B Cells fromHymenolepis diminuta–Infected Mice Ameliorate Colitis Independent of T Cells and via Cooperation with Macrophages

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

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

Cited by 90 publications

References 49 publications

Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 + Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis

Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 + Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis

Splenic B Cells fromHymenolepis diminuta–Infected Mice Ameliorate Colitis Independent of T Cells and via Cooperation with Macrophages

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

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Product

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Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 ⁺ Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis

Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 ⁺ Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis