Abstract
There is an epidemic of immune-mediated disease in highly-developed industrialized countries. Such diseases, like inflammatory bowel disease, multiple sclerosis and asthma increase in prevalence as populations adopt modern hygienic practices. These practices prevent exposure to parasitic worms (helminths). Epidemiologic studies suggest that people who carry helminths have less immune-mediated disease. Mice colonized with helminths are protected from disease in models of colitis, encephalitis, Type 1 diabetes and asthma. Clinical trials show that exposure to helminths reduce disease activity in patients with ulcerative colitis or Crohn’s disease. This chapter reviews some of the work showing that colonization with helminths alters immune responses, against dysregulated inflammation. These helminth-host immune interactions have potentially important implications for the treatment of immune-mediated diseases.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Elliott DE, Urban JFJ, Argo CK et al. Does the failure to acquire helminthic parasites predispose to Crohns disease? FASEB Journal 2000; 14(12):1848–1855.
Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence and environmental influences. Gastroenterology 2004; 126(6): 1504–1517.
Lakatos L, Mester G, Erdelyi Z et al. Striking elevation in incidence and prevalence of inflammatory bowel disease in a province of western Hungary between 1977–2001. World Journal of Gastroenterology 2004; 10(3):404–409.
Marrie RA. Environmental risk factors inmultiple sclerosisaetiology. Lancet Neurol 2004; 3(12):709–718.
Cabre P, Signate A, Olindo S et al. Role of return migration in the emergence of multiple sclerosis in the French West Indies. Brain 2005; 128(Pt12):2899–2910.
Onkamo P, Vaananen S, Karvonen M et al. Worldwide increasein incidence of TypeI diabetes-the analysis of the data on published incidence trends. Diabetologia 1999; 42(12):1395–1403.
Braman SS. The global burden of asthma. Chest 2006; 130(1 Suppl):4S–12S.
Eldeirawi KM, Persky VW. Associations of acculturation and country of birth with asthma and wheezing in Mexican American youths. J Asthma 2006; 43(4):279–286.
Asher MI, Montefort S, Bjorksten B et al. Worldwide time trends in the prevalence of symptoms of asthma,allergic rhinoconjunctivitisand eczema in childhood: ISAAC phases one and three repeat multicountry cross-sectional surveys. Lancet 2006; 368(9537):733–743.
Goncalves ML, Araujo A, Ferreira LF. Human intestinal parasites in the past: new findings and a review. Memorias do Instituto Oswaldo Cruz 2003; 98 Suppl 1:103–118.
Bethony J, Brooker S, Albonico M et al. Soil-transmitted helminth infections:ascariasis, trichuriasis and hookworm. Lancet 2006; 367(9521):1521–1532.
Crompton DW. How much human helminthiasisis there in the world? J Parasitol 1999; 85(3):397–403.
Vermund SH, MacLeod S. Is pinworm a vanishing infection? Laboratory surveillance in a New York City medical center from 1971 to 1986. Am J Dis Child 1988; 142(5):566–568.
Gale EA. A missing link in the hygiene hypothesis? Diabetologia 2002; 45(4):588–594.
Fleming JO, Cook TD. Multiple Sclerosis and the Hygiene Hypothesis. Neurology 2006; 67(11):2085–2086.
Correale J, Farez M. Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol 2007; 61(2):97–108.
Scrivener S, Yemaneberhan H, Zebenigus M et al. Independent effects of intestinal parasiteinfection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study. Lancet 2001; 358(9292):1493–1499.
Leonardi-Bee J, Pritchard D, Britton J. Asthma and current intestinal parasite infection: systematic review and meta-analysis. Am J Respir Crit Care Med 2006; 174(5):514–523.
van den Biggelaar AH, van Ree R, Rodrigues LC et al. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 2000; 356(9243): 1723–1727.
van den Biggelaar AH, Rodrigues LC, van Ree R et al. Long-term treatment of intestinal helminths increases miteskin-test reactivity in Gabonese schoolchildren. Journal of Infectious Diseases 2004; 189(5):892–900.
Araujo MI, Hoppe BS, Medeiros M Jr et al. Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases. Mem Inst Oswaldo Cruz 2004; 99(5 Suppl 1):27–32.
Elliott D, Li J, Blum A et al. Exposure to schistosome eggs protects mice from TNBS-induced colitis. American Journal of Physiology 2003; 284:G385–G391.
Khan WI, Blennerhasset PA, Varghese AK et al. Intestinal nematode infection ameliorates experimental colitis in mice. Infection and Immunity 2002; 70(11):5931–5937.
Moreels TG, Nieuwendijk RJ, De Man JG et al. Concurrent infection with Schistosomamansoni attenuates inflammation induced changes in colonic morphology,cytokine levels and smoothmuscle contractility of trinitrobenzene sulphonic acid induced colitis in rats. Gut 2004; 53(1):99–107.
Hunter MM, Wang A, Hirota CL et al. Neutralizing anti-IL-10 antibody blocks the protective effect of tapeworm infection in a murine model of chemically induced colitis. Journal of Immunology 2005; 174(11):7368–7375.
Setiawan T, Metwali A, Blum AM et al. Heligmosomoides polygyrus promotes regulatory T-cell cytokine production in normal distal murine intestine. Infect Immun 2007; 75(9):4655–4663.
Ince MN, Elliott DE, Setiawan T et al. Heligmosomoides polygyrus induces TLR4 on murine mucosal T-cells that produce TGFbeta after lipopolysaccharide stimulation. Journal of Immunology 2006; 176(2):726–729.
Metwali A, Setiawan T, Blum AM et al. Induction of CD8+ regulatory T-cells in the intestine by Heligmosomoides polygyrus infection. Am J Physiol Gastrointest Liver Physiol 2006; 291(2):G253–G259.
Sellon RK, Tonkonogy S, Schultz M et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immunesystem activation in interleukin-10-deficient mice. Infection and Immunity 1998; 66(11):5224–5231.
Elliott DE, Setiawan T, Metwali A et al. Heligmosomoides polygyrus inhibits establishedcolitis in IL-10-deficient mice. European Journal of Immunology 2004; 34(10):2690–2698.
Sewell D, Qing Z, Reinke E et al. Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. International Immunology 2003; 15(1):59–69.
La Flamme AC, Ruddenklau K, Backstrom BT. Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infection and Immunity 2003; 71(9):4996–5004.
Cooke A, Tonks P, Jones FM et al. Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in nonobese diabetic mice. Parasite Immunology 1999; 21(4):169–176.
Zaccone P, Fehervari Z, Jones FM et al. Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of Type 1 diabetes. Eur J Immunol 2003; 33(5):1439–1449.
Zaccone P, Fehervari Z, Phillips JM et al. Parasitic worms andinflammatorydiseases. Parasite Immunology 2006; 28(10):515–523.
Mangan NE, Van RN, McKenzie AN et al. Helminth-modified pulmonary immune response protects mice from allergen-induced airway hyperresponsiveness. J Immunol 2006;176(1): 138–147.
Wilson MS, Taylor MD, Balk A et al. Suppression of allergic airway inflammation by helminth-induced regulatory T-cells. Journal of Experimental Medicine 2005; 202(9):1199–1212.
Kitagaki K, Businga TR, Racila D et al. Intestinal helminths protect in a murinemodel of asthma. J Immunol 2006; 177(3):1628–1635.
Schnoeller C, Rausch S, Pillai S et al. A Helminth Immunomodulator Reduces Allergie and Inflammatory Responses by Induction of IL-10-Producing Macrophages. J Immunol 2008;180(6):4265–4272.
Melendez AJ, Harnett MM, Pushparaj PN et al. Inhibition of Fe epsilon RI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes. Nat Med 2007; 13(11):1375–1381.
Doetze A, Satoguina J, Burchard G et al. Antigen-specific cellularhyporesponsivenessin a chronic human helminth infection is mediated by T(h)3/T(r)l-type cytokines IL-10 and transforming growth factor-beta butnot by a T(h)l to T(h)2 shift. International Immunology 2000; 12(5):623–630.
Buening J, Homann N, Von SD et al. Helminths as Governors of Inflammatory Bowel Disease. Gut 2008; 57(8):1182–1183.
Hotez PJ, Brooker S, Bethony JM et al. Hookworm infection. N Engl J Med 2004; 351(8):799–807.
Pritchard DI, Brown A. Is Necator americanus approaching a mutualistic symbiotic relationship with humans? Trends in Parasitology 2001; 17(4):169–172.
Maxwell C, Hussain R, Nutman TB et al. The clinical and immunologic responses of normal human volunteers to low dose hookworm (Necator americanus) infection. Am J Trop Med Hyg 1987; 37(1):126–134.
Möhrs K, Harris DP, Lund FE et al. Systemic dissemination and persistence of Th2 and Type 2 cells in response to infection with a strictly enteric nematode parasite. J Immunol 2005;175(8):5306–5313.
Croese J, O’neil J, Masson J et al. A proof of concept study establishing Necator americanus in Crohn’s patientsand reservoir donors. Gut 2006; 55(1):136–137.
Mortimer K, Brown A, Feary J et al. Dose-ranging study for trials of therapeutic infection with Necator americanus in humans. Am J Trop Med Hyg 2006; 75(5):914–920.
Falcone FH, Pritchard DI. Parasite role reversal: worms on trial. Trends Parasitol 2005; 21(4): 157–60.
Beer RJ. The relationship between Trichuris trichiura (Linnaeus 1758) of man and Trichuris suis (Schrank 1788) of the pig. Research in Veterinary Science 1976;20(1):47–54.
Summers RW, Elliott DE, Qadir K et al. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. American Journal of Gastroenterology 2003; 98(9):2034–2041.
Summers RW, Elliott DE, Urban JF Jr et al. Trichurissuis therapyinCrohn’s disease. Gut 2005; 54(1):87–90.
Summers RW, Elliott DE, Urban JF Jr et al. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 2005;128(4):825–832.
Elliott DE, Summers RW, Weinstock JV. Helminths andthe modulation of mucosal inflammation. CurrentOpinion in Gastroenterology 2005; 21(1):51–58.
Siegel CA, Hur C, Korzenik JR et al. Risksand benefits of infliximabfor thetreatment of Crohn’s disease. Clin Gastroenterol Hepatol 2006; 4(8):1017–1024.
Chen CC, Louie S, McCormick B et al. Concurrentinfection withan intestinal helminth parasite impairs host resistance to enteric Citrobacter rodentium and enhances Citrobacter-induced colitis in mice. Infect Immun 2005; 73(9):5468–5481.
Chen CC, Louie S, McCormick BA et al. Helminth-primed dendritic cells alter the host response to enteric bacterial infection. J Immunol 2006; 176(1):472–483.
Weng M, Huntley D, Huang IF et al. Alternatively activated macrophages in intestinal helminth infection: effectson concurrent bacterial colitis. J Immunol 2007; 179(7):4721–4731.
Mansfield LS, Gauthier DT, Abner SR et al. Enhancement of disease and pathology by synergy of Trichuris suis and Campylobacter jejuni in the colon of immunologically naive swine. Am J Trop Med Hyg 2003; 68(1):70–80.
Karp CL, Auwaerter PG. Coinfection with HIV and tropical infectious diseases. II. Helminthic, fungal, bacterial and viral pathogens. Clin Infect Dis 2007; 45(9):1214–1220.
Mitreva M, Blaxter ML, Bird DM et al. Comparative genomics of nematodes. Trends Genet 2005; 21(10):573–581.
Hunter MM, Wang A, McKay DM. Helminth infectionenhances disease in a murine TH2 model of colitis. Gastroenterology 2007; 132(4): 1320–1330.
Reardon C, Sanchez A, Hogaboam CM et al. Tapeworm infectionreduces epithelialion transport abnormalitiesinmurine dextran sulfate sodium-induced colitis. Infection and Immunity 2001; 69(7):4417–4423.
Smith P, Mangan NE, Walsh CM et al. Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol 2007; 178(7):4557–4566.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Elliott, D.E., Weinstock, J.V. (2009). Helminthic Therapy: Using Worms to Treat Immune-Mediated Disease. In: Fallon, P.G. (eds) Pathogen-Derived Immunomodulatory Molecules. Advances in Experimental Medicine and Biology, vol 666. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1601-3_12
Download citation
DOI: https://doi.org/10.1007/978-1-4419-1601-3_12
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-1600-6
Online ISBN: 978-1-4419-1601-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)