Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-29T09:10:39.014Z Has data issue: false hasContentIssue false
  • English
  • Français

Therapeutic immunomodulators from nematode parasites

Published online by Cambridge University Press:  19 June 2008

William Harnett  and
Margaret M. Harnett
William Harnett*
Affiliation:
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
Margaret M. Harnett
Affiliation:
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow, G12 8TA, UK.
*
*Corresponding author: William Harnett, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, UK. Tel.: +44 141 548 3725; Fax: +44 141 552 2562; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

There has been an alarming increase in the incidence of autoimmune and allergic diseases in Western countries in the past few decades. However, in countries endemic for parasitic helminth infections, such diseases remain relatively rare. Hence, it has been hypothesised that helminths may protect against the development of autoimmunity and allergy. This article reviews the evidence supporting this idea with respect to helminths of the phylum Nematoda (nematodes), considering data from human studies and animal models of inflammatory disease. The nature and mode of action of nematode-derived molecules with immunomodulatory properties are considered, and their therapeutic efficacy in models of autoimmunity and allergy described. The recent and future use of nematodes and their products in treating human disease are also discussed.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e18
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Schmidt, G.S. and Roberts, L.S. (1989) Foundations of Parasitology (4th edn), pp. 379-405, McGraw-HillGoogle Scholar
2Schmidt, G.S. and Roberts, L.S. (1989) Foundations of Parasitology (4th edn), pp. 488-503, McGraw-HillGoogle Scholar
3Schmidt, G.S. and Roberts, L.S. (1989) Foundations of Parasitology (4th edn), pp. 451-463, McGraw-HillGoogle Scholar
4Schmidt, G.S. and Roberts, L.S. (1989) Foundations of Parasitology (4th edn), pp. 416-427, McGraw-HillGoogle Scholar
5Schmidt, G.S. and Roberts, L.S. (1989) Foundations of Parasitology (4th edn), pp. 434-450, McGraw-HillGoogle Scholar
6Subramanian, S. et al. (2004) The dynamics of Wuchereria bancrofti infection: a model-based analysis of longitudinal data from Pondicherry, India. Parasitology 128, 467-482CrossRefGoogle ScholarPubMed
7Nutman, T.B and Kumaraswami, V. (2001) Regulation of the immune response in lymphatic filariasis: perspectives on acute and chronic infection with Wuchereria bancrofti in South India. Parasit Immunol 28, 389-399CrossRefGoogle Scholar
8Nakamura, T. et al. (1997) Polarization of IL-4 and IFN-γ-producing CD4+ T cells following activation of naïve CD4+ T cells. J Immunol 158, 1085-1094CrossRefGoogle ScholarPubMed
9Moore, K.W. et al. (2001) Interleukin 10 and the interleukin 10 receptor. Ann Rev Immunol 19, 683-765CrossRefGoogle ScholarPubMed
10Rajan, T.V. (2005) Natural course of lymphatic filariasis: insights from epidemiology, experimental human infections and clinical observations. Am J Trop Med Hyg 285, 995-998CrossRefGoogle Scholar
11Bradley, J.E. and Jackson, J.A. (2004) Immunity, immunoregulation and the ecology of trichuriasis and ascariasis. Parasit Immunol 26, 429-441CrossRefGoogle ScholarPubMed
12van Riet, E., Hartgers, F.C. and Yazdanbakhsh, M. (2007) Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiol 212, 475-490CrossRefGoogle ScholarPubMed
13Wills-Karp, M., Santeliz, J. and Karp, C.L. (2001) The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol 1, 69-75CrossRefGoogle ScholarPubMed
14Elliott, D.E., Summers, R.W. and Weinstock, J.V. (2007) Helminths as governors of immune-mediated inflammation. Int J Parasitol 37, 457-464CrossRefGoogle ScholarPubMed
15Busse, W.W. and Lemanske, R.F. (2001) Asthma. N Eng J Med 344, 350-362CrossRefGoogle ScholarPubMed
16Cooper, P.J. (2004) Intestinal worms and human allergy. Parasit Immunol 26, 455-469CrossRefGoogle ScholarPubMed
17Falcone, F.H. and Pritchard, D.I. (2005) Parasite role reversal: worms on trial. TRENDS Parasitol 21, 157-160CrossRefGoogle ScholarPubMed
18Maizels, R.M. (2005) infections and allergy – helminths, hygiene and host immune regulation. Curr Opin Immunol 17, 656-661CrossRefGoogle ScholarPubMed
19Hagel, I. et al. (1993) Allergic reactivity of children of different socioeconomic levels in tropical populations. Int Arch Allergy Immunol 101, 209-214CrossRefGoogle ScholarPubMed
20Lynch, N.R. et al. (1993) Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum. J Allergy Clin Immunol 92, 404-411CrossRefGoogle Scholar
21Selassie, P.G. et al. (2000) Total and specific IgE (house dust mite and intestinal helminths) in asthmatics and controls from Gondar, Ethiopia. Clin Exp Allergy 30, 356-358CrossRefGoogle ScholarPubMed
22Nyan, O.A. et al. (2001) Atopy, intestinal helminth infection and total serum IgE in rural and urban adult Gambian communities, Clin Exp Allergy 31, 1672-1678CrossRefGoogle Scholar
23Scrivener, S. et al. (2001) Independent effects of intestinal parasite infection and domestic allergen exposure on the risk of wheeze in Ethiopia: a nested case-control study. Lancet 358, 1493-1499CrossRefGoogle Scholar
24Cooper, P.J. et al. (2003) Reduced risk of atopy among school age children infected with geohelminth parasites in a rural area of the tropics. J Allergy Clin Immunol 111, 995-1000CrossRefGoogle Scholar
25Dagoye, D. et al. (2003) Wheezing, allergy and parasite infection in children in urban and rural Ethiopia. Am J Respir Crit Care Med 167, 1369-1373CrossRefGoogle Scholar
26van den Biggelaer, A.H.J. et al. (2004) Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren. J Infect Dis 189, 892-900CrossRefGoogle Scholar
27Flohr, C. et al. (2006) Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: a cross-sectional study. J Allergy Clin Immunol 118, 1305-1311CrossRefGoogle ScholarPubMed
28Hunter, M.M. and McKay, D.M. (2004) Helminths as therapeutic agents for inflammatory bowel disease. Aliment Pharmacol Ther 19, 167-177CrossRefGoogle ScholarPubMed
29Zaccone, P. et al. (2006) Parasitic worms and inflammatory diseases. Parasit Immunol 28, 515-525CrossRefGoogle ScholarPubMed
30Reddy, A. and Fried, B. (2007) The use of Trichuris suis and other helminth therapies to treat Crohn's disease. Parasitol Res 100, 921-927CrossRefGoogle ScholarPubMed
31Aoyama, H. et al. (2007) An inverse relationship between autoimmune liver diseases and Strongyloides stercoralis infection. Am J Trop Med Hyg 76, 972-976CrossRefGoogle ScholarPubMed
32Wang, C.C. et al. (2001) Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin. Clin Expl Allergy 31, 495-503CrossRefGoogle ScholarPubMed
33Bashir, M.E. et al. (2002) An enteric helminth infection protects against an allergic response to dietary antigen. J Immunol 169, 3284-3292CrossRefGoogle ScholarPubMed
34Wohlleben, G. et al. (2004) Helminth infection modulates the development of allergen-induced airway inflammation. Int Immunol 16, 585-596CrossRefGoogle ScholarPubMed
35Wilson, M.S. et al. (2005) Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med 202, 1199-1212CrossRefGoogle ScholarPubMed
36Kitagaki, K. et al. (2006) Intestinal helminths protect in a murine model of asthma. J Immunol 177, 1628-1635CrossRefGoogle Scholar
37Elliott, D.E. et al. (2000) Does the failure to acquire helminth parasites predispose to Crohn's disease? FASEB J 14, 1848-1855CrossRefGoogle ScholarPubMed
38Khan, W.I. et al. (2002) intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun 70, 5931-5937CrossRefGoogle ScholarPubMed
39Elliott, D.E. et al. (2004) Heligomosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Eur J Immunol 34, 2690-2698CrossRefGoogle Scholar
40Saunders, K.A. et al. (2007) Inhibition of autoimmune Type 1 diabetes by gastrointestinal helminth infection. Infect Immun 75, 397-407CrossRefGoogle ScholarPubMed
41Finkelman, F. et al. (1997) Cytokine regulation of host defence against parasitic gastrointestinal nematodes: lessons from studies with rodent models. Ann Rev Immunol 15, 503-533CrossRefGoogle ScholarPubMed
42Diaz, A. and Allen, J.E. (2007) Mapping immune response profiles: the emerging scenario from helminth immunology. Eur J Immunol 37, 3319-3326CrossRefGoogle ScholarPubMed
43Banchereau, J. et al. (2000) Immunobiology of dendritic cells. Ann Rev Immunol 18, 767-811CrossRefGoogle ScholarPubMed
44Whelan, M. et al. (2000) A filarial nematode secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells. J Immunol 164, 6453-6460CrossRefGoogle ScholarPubMed
45Balic, A. et al. (2004) Selective maturation of dendritic cells by Nippostrongylus brasiliensis-secreted proteins drives Th2 immune responses. Eur J Immunol 34, 3047-3059CrossRefGoogle ScholarPubMed
46Harnett, W. and Harnett, M.M. (2006) Molecular basis of worm-induced immunomodulation. Parasit Immunol 28, 535-543CrossRefGoogle ScholarPubMed
47Gause, W.C., Urban, J.F.Jr. and Stadecker, M.J. (2003) The immune response to parasitic helminths: insights from murine models. Trends Immunol 24, 269-277CrossRefGoogle ScholarPubMed
48Scales, H.E. et al. (2004) Effect of inducible costimulator blockade on the pathological and protective immune responses induced by the gastrointestinal helminth Trichinella spiralis. Eur J Immunol 34, 2854-2862CrossRefGoogle ScholarPubMed
49Liblau, R.S., Singer, S.M. and McDevitt, H.O. (1995) TH1 and TH2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Imm Today 16, 34-38CrossRefGoogle ScholarPubMed
50Taylor, M.D. et al. (2007) CTLA-4 and CD4+ CD25+ regulatory T cells inhibit protective immunity to filarial parasites in vivo. J Immunol 179, 4626-4634CrossRefGoogle ScholarPubMed
51Carvalho, E.M., Bastos, L.S. and Araujo, M.I. (2006) Worms and Allergy. Parasit Immunol 28, 525-534CrossRefGoogle ScholarPubMed
52Metwali, A. et al. (2006) Induction of CD8+ regulatory T cells in the intestine by Heligosomoides polygyrus infection. Am J Physiol Gastrointest Liver Physiol 291, G253-G259CrossRefGoogle Scholar
53Ince, M.N. et al. (2006) Heligomosomoides polygyrus induces TLR4 on murine mucosal T cells that produce TGFbeta after lipopolysaccharide stimulation. J Immunol 176, 726-729CrossRefGoogle Scholar
54Erb, K.J. (2007) Helminths, allergic disorders and IgE-mediated immune responses: where do we stand? Eur J Immunol 37, 1170-1173CrossRefGoogle ScholarPubMed
55Pochanke, V. et al. (2007) Identification and characterisation of a novel antigen from the nematode Nippostrongylus brasiliensis recognised by specific IgE. Eur J Immunol 37, 1275-1284CrossRefGoogle ScholarPubMed
56Mitre, E., Norwood, S. and Nutman, T.B. (2005) Saturation of immunoglobulin E (IgE) binding sites by polyclonal IgE does not explain the protective effect of helminth infections against atopy. Infect Immun 73, 4106-4111CrossRefGoogle Scholar
57Hussain, R., Poindexter, R.W. and Ottesen, E.A. (1992) Control of allergic reactivity in human filariasis: predominant localization of blocking antibody to the IgG4 subclass. J Immunol 148, 2731-2737.CrossRefGoogle Scholar
58Royer, B. et al. (2001) Inhibition of IgE-induced activation of human mast cells by IL-10. Clin Exp Allerg 31, 694-704CrossRefGoogle ScholarPubMed
59Kennedy Norton, S. et al. (2008) IL-10 suppresses mast cell IgE receptor expression and signalling in vitro and in vivo. J Immunol 180, 2848-2854CrossRefGoogle ScholarPubMed
60Kashyap, M. et al. (2008) CD4 T cell-mast cell interactions alter IgE receptor expression and signalling. J Immunol 180, 2039-2043CrossRefGoogle Scholar
61Trujillo-Vargas, C.M. et al. (2007) Helminth derived products inhibit the development of allergic responses in mice. Am J Respir Crit Care Med 175, 336-344CrossRefGoogle ScholarPubMed
62Keir, P.A. et al. (2004) Inhibition of neutrophil recruitment by ES of nippostrongylus brasiliensis. Parasit Immunol 26, 137-140CrossRefGoogle ScholarPubMed
63Lima, C. et al. (2002) Eosinophilic inflammation and airway hyper-responsiveness are profoundly inhibited by a helminth (Ascaris suum) extract in a murine model of asthma. Clin Exp Allergy 32, 1659-1666CrossRefGoogle Scholar
64Itami, D.M. et al. (2005) Modulation of murine experimental asthma by Ascaris suum components. Clin Exp Allergy 38, 873-879CrossRefGoogle Scholar
65Oshiro, T.M., Macedo, M.S. and Macedo-Soares, M.F. (2005) Anti-inflammatory activity of PAS-1, a protein component of Ascaris suum. Inflamm Res 54, 17-21CrossRefGoogle ScholarPubMed
66Imai, S. and Fujita, K. (2004) Molecules of parasites as immunomodulatory drugs. Curr Top Med Chem 4, 539-560CrossRefGoogle ScholarPubMed
67Harnett, W. and Harnett, M.M. (2006) Filarial nematode secreted product ES-62 is an anti-inflammatory agent: therapeutic potential of small molecule derivatives and ES-62 peptide mimetics. Clin Exp Phar Phys 33, 511-518CrossRefGoogle ScholarPubMed
68McInnes, I.B. et al. (2003) A novel therapeutic approach targeting articular inflammation using the filarial nematode-derived phosphorylcholine-containing glycoprotein ES-62. J Immunol 171, 2127-2133CrossRefGoogle ScholarPubMed
69Melendez, A.J. et al. (2007) Inhibition of FcɛRI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes. Nat Med 13, 1375-1381CrossRefGoogle Scholar
70Harnett, M.M. et al. (2007) The phosphorylcholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis. Annal Rheum Dis 67, 518-523CrossRefGoogle ScholarPubMed
71Kollis, J.K. and Linden, A. (2004) Interleukin 17 family members and inflammation. Immunity 21, 467-478CrossRefGoogle Scholar
72Nakae, S., Nambu, A., Sudo, K. and Iwakura, Y. (2003) Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol 171, 6173-6177CrossRefGoogle ScholarPubMed
73Croese, J. et al. (2006) A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors. Gut 55, 136-137CrossRefGoogle ScholarPubMed
74Stassens, P. et al. (1996) Anticoagulent repertoire of the hookworm Ancylostoma caninum. Proc Natl Acad Sci U S A 93, 2149-2154CrossRefGoogle Scholar
75Moons, A.H. et al. (2003) Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, inpatients in patients undergoing elective coronary angioplasty. J Am Coll Cardiol 41, 2147-2153CrossRefGoogle Scholar
76Lee, A. et al. (2001) Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anti-coagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement. Circulation 104, 74-78CrossRefGoogle ScholarPubMed
77Giugliano, R.P. et al. (2007) Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol 49, 2398-2407CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

The nematode pages of the Cambridge University Schistosomiasis Research Group website provide background information on the various species:

Schmidt, G.S. and Roberts, L.S. (2004) Foundations of Parasitology (7th edn), McGraw-HillGoogle Scholar
http://www.path.cam.ac.uk/~schisto/General_Parasitology/Hm.helminths.htmlGoogle Scholar
http://en.wikipedia.org/wiki/Helminthic_therapyGoogle Scholar
Schmidt, G.S. and Roberts, L.S. (2004) Foundations of Parasitology (7th edn), McGraw-HillGoogle Scholar
http://www.path.cam.ac.uk/~schisto/General_Parasitology/Hm.helminths.htmlGoogle Scholar
http://en.wikipedia.org/wiki/Helminthic_therapyGoogle Scholar