Skip to main content

Can the Study of Helminths Be Fruitful for Human Diseases?

  • Chapter
  • First Online:
Helminth Infections and their Impact on Global Public Health

Abstract

Parasitic helminths have an inclination to be long-lived invaders with certain human parasites reported as surviving for in excess of a decade. Such longevity tends to be associated with an apparent lack of pathology and one contributor to this perhaps somewhat surprising situation is likely to be the secretion of anti-inflammatory immunomodulators by the worms. Such molecules act to dampen and effect the polarization of immune responses and this invariably potent immunomodulation frequently extends to responses to third party antigens, vaccines and other diseases. Relating to the latter, a particularly serendipitous consequence of worm infection that is being increasingly recognized, is its effect on human conditions that are associated with aberrant inflammation. For this reason, helminths have within the last decade attracted substantial attention in the research community as a potential source of novel therapies against allergic and autoimmune diseases. In this article we describe the effects of helminths on five such diseases—asthma, rheumatoid arthritis, multiple sclerosis, type I diabetes and inflammatory bowel disease. In particular, we consider the immunological mechanisms that underlie helminth-mediated protection against these diseases and in addition, highlight individual helminth molecules that may have therapeutic potential.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Allen JE, Maizels RM (2011) Diversity and dialogue in immunity to helminths. Nat Rev Immunol 11:375–88

    CAS  PubMed  Google Scholar 

  • Amu S, Saunders SP, Kronenberg M, Mangan NE, Atzberger A, Fallon PG (2010) Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model. J Allergy Clin Immunol 125:1114–1124

    CAS  PubMed  Google Scholar 

  • Anthony RM, Rutitzky LI, Urban JF Jr, Stadecker MJ, Gause WC (2007) Protective immune mechanisms in helminth infection. Nat Rev Immunol 7:975–87

    CAS  PubMed Central  PubMed  Google Scholar 

  • Aranzamendi C, Fransen F, Langelaar M, Franssen F, van der Ley P, van Putten JP et al (2012) Trichinella spiralis-secreted products modulate DC functionality and expand regulatory T cells in vitro. Parasite Immunol 34:210–23

    CAS  PubMed  Google Scholar 

  • Aranzamendi C, de Bruin A, Kuiper R, Boog CJ, van Eden W, Rutten V et al (2013) Protection against allergic airway inflammation during the chronic and acute phases of Trichinella spiralis infection. Clin Exp Allergy 43:103–15

    CAS  PubMed  Google Scholar 

  • Araújo CA, Perini A, Martins MA, Macedo MS, Macedo-Soares MF (2008) PAS-1, a protein from Ascaris suum, modulates allergic inflammation via IL-10 and IFN-gamma, but not IL-12. Cytokine 44:335–41

    PubMed  Google Scholar 

  • Bager P, Vinkel Hansen A, Wohlfahrt J, Melbye M (2012) Helminth infection does not reduce risk for chronic inflammatory disease in a population-based cohort study. Gastroenterology 142:55–62

    PubMed  Google Scholar 

  • Bhargava P, Li C, Stanya KJ, Jacobi D, Dai L, Liu S et al (2012) Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways. Nat Med 18:1665–72

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blum AM, Hang L, Setiawan T, Urban JP Jr, Stoyanoff KM, Leung J et al (2012) Heligmosomoides polygyrus bakeri induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut T cell responses. J Immunol 189:2512–20

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bodammer P, Waitz G, Loebermann M, Holtfreter MC, Maletzki C, Krueger MR et al (2011) Schistosoma mansoni infection but not egg antigen promotes recovery from colitis in outbred NMRI mice. Dig Dis Sci 56:70–8

    PubMed  Google Scholar 

  • Cançado GG, Fiuza JA, de Paiva NC, Lemos Lde C, Ricci ND, Gazzinelli-Guimarães PH et al (2011) Hookworm products ameliorate dextran sodium sulfate-induced colitis in BALB/c mice. Inflamm Bowel Dis 17:2275–86

    PubMed  Google Scholar 

  • Cardoso LS, Oliveira SC, Góes AM, Oliveira RR, Pacífico LG, Marinho FV et al (2010) Schistosoma mansoni antigens modulate the allergic response in a murine model of ovalbumin-induced airway inflammation. Clin Exp Immunol 160:266–74

    CAS  PubMed Central  PubMed  Google Scholar 

  • Carranza F, Falcón CR, Nuñez N, Knubel C, Correa SG, Bianco I et al (2012) Helminth antigens enable CpG-activated dendritic cells to inhibit the symptoms of collagen-induced arthritis through Foxp3+ regulatory T cells. PLoS One 7:e40356

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chiuso-Minicucci F, VAN DB, Zorzella-Pezavento SF, Peres RS, Ishikawa LL, Rosa LC et al (2011) Experimental autoimmune encephalomyelitis evolution was not modified by multiple infections with Strongyloides venezuelensis. Parasite Immunol 33(5):303–8

    CAS  PubMed  Google Scholar 

  • Cho MK, Lee CH, Yu HS (2011) Amelioration of intestinal colitis by macrophage migration inhibitory factor isolated from intestinal parasites through toll-like receptor 2. Parasite Immunol 33:265–75

    CAS  PubMed  Google Scholar 

  • Cooke A, Tonks P, Jones FM, O’Shea H, Hutchings P, Fulford AJ et al (1999) Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol 21:169–76

    CAS  PubMed  Google Scholar 

  • Correale J, Farez M (2007) Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol 61:97–108

    CAS  PubMed  Google Scholar 

  • Correale J, Farez M (2009) Helminth antigens modulate immune responses in cells from multiple sclerosis patients through TLR2-dependent mechanisms. J Immunol 183:5999–6012

    CAS  PubMed  Google Scholar 

  • Correale J, Farez MF (2011) The impact of parasite infections on the course of multiple sclerosis. J Neuroimmunol 233:6–11

    CAS  PubMed  Google Scholar 

  • Daniłowicz-Luebert E, Steinfelder S, Kühl AA, Drozdenko G, Lucius R, Worm M et al (2013) A nematode immunomodulator suppresses grass pollen-specific allergic responses by controlling excessive Th2 inflammation. Int J Parasitol 43:201–10

    PubMed  Google Scholar 

  • Dittrich AM, Erbacher A, Specht S, Diesner F, Krokowski M, Avagyan A et al (2008) Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model. J Immunol 180:1792–9

    CAS  PubMed  Google Scholar 

  • Donskow-Łysoniewska K, Krawczak K, Doligalska M (2012a) Heligmosomoides polygyrus: EAE remission is correlated with different systemic cytokine profiles provoked by L4 and adult nematodes. Exp Parasitol 132:243–8

    PubMed  Google Scholar 

  • Donskow-Łysoniewska K, Majewski P, Brodaczewska K, Jóźwicka K, Doligalska M (2012b) Heligmosmoides polygyrus fourth stages induce protection against DSS-induced colitis and change opioid expression in the intestine. Parasite Immunol 34:536–46

    PubMed  Google Scholar 

  • Du L, Tang H, Ma Z, Xu J, Gao W, Chen J et al (2011) The protective effect of the recombinant 53-kDa protein of Trichinella spiralis on experimental colitis in mice. Dig Dis Sci 56:2810–7

    CAS  PubMed  Google Scholar 

  • Elliott DE, Weinstock JV (2012) Helminth-host immunological interactions: prevention and control of immune-mediated diseases. Ann N Y Acad Sci 1247:83–96

    CAS  PubMed Central  PubMed  Google Scholar 

  • Elliott DE, Li J, Blum A, Metwali A, Qadir K, Urban JF Jr et al (2003) Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol 284:G385–91

    CAS  PubMed  Google Scholar 

  • Elliott DE, Setiawan T, Metwali A, Blum A, Urban JF Jr, Weinstock JV (2004) Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Eur J Immunol 34:2690–8

    CAS  PubMed  Google Scholar 

  • Elliott DE, Metwali A, Leung J, Setiawan T, Blum AM, Ince MN et al (2008) Colonization with Heligmosomoides polygyrus suppresses mucosal IL-17 production. J Immunol 181:2414–9

    CAS  PubMed  Google Scholar 

  • Espinoza-Jiménez A, Rivera-Montoya I, Cárdenas-Arreola R, Morán L, Terrazas LI (2010) Taenia crassiceps infection attenuates multiple low-dose streptozotocin-induced diabetes. J Biomed Biotechnol 2010:850541

    PubMed Central  PubMed  Google Scholar 

  • Ferreira I, Smyth D, Gaze S, Aziz A, Giacomin P, Ruyssers N et al (2013) Hookworm excretory/secretory products induce interleukin-4 (IL-4)+ IL-10+ CD4+ T cell responses and suppress pathology in a mouse model of colitis. Infect Immun 81:2104–11

    CAS  PubMed Central  PubMed  Google Scholar 

  • Flowers S, Hopkins M (2013) Autoimmune disease: patients self-treat with parasitic worms. Nature 493:163

    CAS  PubMed  Google Scholar 

  • Grainger JR, Smith KA, Hewitson JP, McSorley HJ, Harcus Y, Filbey KJ et al (2010) Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-β pathway. J Exp Med 207:2331–41

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gruden-Movsesijan A, Ilic N, Mostarica-Stojkovic M, Stosic-Grujicic S, Milic M, Lj S-M (2008) Trichinella spiralis: modulation of experimental autoimmune encephalomyelitis in DA rats. Exp Parasitol 118:641–647

    CAS  PubMed  Google Scholar 

  • Gruden-Movsesijan A, Ilic N, Mostarica-Stojkovic M, Stosic-Grujicic S, Milic M, Sofronic-Milosavljevic L (2010) Mechanisms of modulation of experimental autoimmune encephalomyelitis by chronic Trichinella spiralis infection in Dark Agouti rats. Parasite Immunol 32:450–9

    CAS  PubMed  Google Scholar 

  • Hamid F, Wiria AE, Wammes LJ, Kaisar MM, Djuardi Y, Versteeg SA, Wahyuni S, van Ree R, Sartono E, Supali T, Yazdanbakhsh M (2013) Risk Factors Associated with the Development of Atopic Sensitization in Indonesia. PLoS One 8:e67064

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hang L, Setiawan T, Blum AM, Urban J, Stoyanoff K, Arihiro S et al (2010) Heligmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity. J Immunol 185:3184–9

    CAS  PubMed Central  PubMed  Google Scholar 

  • Harnett W, Harnett MM (2010) Helminth-derived immunomodulators: can understanding the worm produce the pill? Nat Rev Immunol 10:278–84

    CAS  PubMed  Google Scholar 

  • Harnett MM, Kean DE, Boitelle A, McGuiness S, Thalhamer T, Steiger CN et al (2008) The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis. Ann Rheum Dis 67:518–23

    CAS  PubMed  Google Scholar 

  • Hartmann S, Schnoeller C, Dahten A, Avagyan A, Rausch S, Lendner M et al (2009) Gastrointestinal nematode infection interferes with experimental allergic airway inflammation but not atopic dermatitis. Clin Exp Allergy 39:1585–96

    CAS  PubMed  Google Scholar 

  • Hayes KS, Bancroft AJ, Grencis RK (2004) Immune-mediated regulation of chronic intestinal nematode infection. Immunol Rev 201:75–88

    CAS  PubMed  Google Scholar 

  • He Y, Li J, Zhuang W, Yin L, Chen C, Li J et al (2010) The inhibitory effect against collagen-induced arthritis by Schistosoma japonicum infection is infection stage-dependent. BMC Immunol 11:28

    PubMed Central  PubMed  Google Scholar 

  • Hübner MP, Stocker JT, Mitre E (2009) Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells. Immunology 127:512–22

    PubMed Central  PubMed  Google Scholar 

  • Hübner MP, Shi Y, Torrero MN, Mueller E, Larson D, Soloviova K et al (2012) Helminth protection against autoimmune diabetes in nonobese diabetic mice is independent of a type 2 immune shift and requires TGF-β. J Immunol 188:559–68

    PubMed Central  PubMed  Google Scholar 

  • Hunter MM, Wang A, Hirota CL, McKay DM (2005) Neutralizing anti-IL-10 antibody blocks the protective effect of tapeworm infection in a murine model of chemically induced colitis. J Immunol 174:7368–75

    CAS  PubMed  Google Scholar 

  • Itami DM, Oshiro TM, Araujo CA, Perini A, Martins MA, Macedo MS et al (2005) Modulation of murine experimental asthma by Ascaris suum components. Clin Exp Allergy 35:873–9

    CAS  PubMed  Google Scholar 

  • Johnston MJ, Wang A, Catarino ME, Ball L, Phan VC, MacDonald JA et al (2010) Extracts of the rat tapeworm, Hymenolepis diminuta, suppress macrophage activation in vitro and alleviate chemically induced colitis in mice. Infect Immun 78:1364–75

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kabeerdoss J, Pugazhendhi S, Subramanian V, Binder HJ, Ramakrishna BS (2011) Exposure to hookworms in patients with Crohn's disease: a case-control study. Aliment Pharmacol Ther 34:923–30

    CAS  PubMed  Google Scholar 

  • Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y et al (2002) Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun 70:5931–7

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kitagaki K, Businga TR, Racila D, Elliott DE, Weinstock JV, Kline JN (2006) Intestinal helminths protect in a murine model of asthma. J Immunol 177:1628–35

    CAS  PubMed  Google Scholar 

  • Kuijk LM, Klaver EJ, Kooij G, van der Pol SM, Heijnen P, Bruijns SC et al (2012) Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation. Mol Immunol 51:210–8

    CAS  PubMed  Google Scholar 

  • La Flamme AC, Ruddenklau K, Bäckström BT (2003) Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immun 71:4996–5004

    PubMed Central  PubMed  Google Scholar 

  • Lee KH, Park HK, Jeong HJ, Park SK, Lee SJ, Choi SH et al (2008) Immunization of proteins from Toxascaris leonina adult worm inhibits allergic specific Th2 response. Vet Parasitol 156:216–25

    CAS  PubMed  Google Scholar 

  • Leung J, Hang L, Blum A, Setiawan T, Stoyanoff K, Weinstock J (2012) Heligmosomoides polygyrus abrogates antigen-specific gut injury in a murine model of inflammatory bowel disease. Inflamm Bowel Dis 18:1447–55

    PubMed  Google Scholar 

  • Lima C, Perini A, Garcia ML, Martins MA, Teixeira MM, Macedo MS (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 32:1659–66

    CAS  PubMed  Google Scholar 

  • Liu Q, Sundar K, Mishra PK, Mousavi G, Liu Z, Gaydo A et al (2009) Helminth infection can reduce insulitis and type 1 diabetes through CD25- and IL-10-independent mechanisms. Infect Immun 77:5347–58

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liu P, Li J, Yang X, Shen Y, Zhu Y, Wang S et al (2010) Helminth infection inhibits airway allergic reaction and dendritic cells are involved in the modulation process. Parasite Immunol 32:57–66

    CAS  PubMed  Google Scholar 

  • McConchie BW, Norris HH, Bundoc VG, Trivedi S, Boesen A, Urban JF Jr et al (2006) Ascaris suum-derived products suppress mucosal allergic inflammation in an interleukin-10-independent manner via interference with dendritic cell function. Infect Immun 74:6632–41

    CAS  PubMed Central  PubMed  Google Scholar 

  • McInnes IB, Leung BP, Harnett M, Gracie JA, Liew FY, Harnett W (2003) A novel therapeutic approach targeting articular inflammation using the filarial nematode-derived phosphorylcholine-containing glycoprotein ES-62. J Immunol 171:2127–33

    CAS  PubMed  Google Scholar 

  • McSorley HJ, O’Gorman MT, Blair N, Sutherland TE, Filbey KJ, Maizels RM (2012) Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus. Eur J Immunol 42:2667–82

    CAS  PubMed  Google Scholar 

  • Melendez AJ, Harnett MM, Pushparaj PN, Wong WS, Tay HK, McSharry CP et al (2007) Inhibition of Fc epsilon RI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes. Nat Med 13:1375–81

    CAS  PubMed  Google Scholar 

  • Melon A, Wang A, Phan V, McKay DM (2010) Infection with Hymenolepis diminuta is more effective than daily corticosteroids in blocking chemically induced colitis in mice. J Biomed Biotechnol 2010:384523

    PubMed Central  PubMed  Google Scholar 

  • Metwali A, Setiawan T, Blum AM, Urban J, Elliott DE, Hang L et al (2006) Induction of CD8+ regulatory T cells in the intestine by Heligmosomoides polygyrus infection. Am J Physiol Gastrointest Liver Physiol 291:G253–9

    CAS  PubMed  Google Scholar 

  • Mishra PK, Patel N, Wu W, Bleich D, Gause WC (2013) Prevention of type 1 diabetes through infection with an intestinal nematode parasite requires IL-10 in the absence of a Th2-type response. Mucosal Immunol 6:297–308

    CAS  PubMed  Google Scholar 

  • Mo HM, Liu WQ, Lei JH, Cheng YL, Wang CZ, Li YL (2007) Schistosoma japonicum eggs modulate the activity of CD4+ CD25+ Tregs and prevent development of colitis in mice. Exp Parasitol 116:385–9

    CAS  PubMed  Google Scholar 

  • Mo HM, Lei JH, Jiang ZW, Wang CZ, Cheng YL, Li YL, Liu WQ (2008) Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice. Parasitol Res 103:1183–9

    PubMed  Google Scholar 

  • Motomura Y, Wang H, Deng Y, El-Sharkawy RT, Verdu EF, Khan WI (2009) Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis. Clin Exp Immunol 155:88–95

    CAS  PubMed Central  PubMed  Google Scholar 

  • Osada Y, Shimizu S, Kumagai T, Yamada S, Kanazawa T (2009) Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regulation of pro-inflammatory mediators. Int J Parasitol 39:457–64

    CAS  PubMed  Google Scholar 

  • Pacífico LG, Marinho FA, Fonseca CT, Barsante MM, Pinho V, Sales-Junior PA et al (2009) Schistosoma mansoni antigens modulate experimental allergic asthma in a murine model: a major role for CD4+ CD25+ Foxp3+ T cells independent of interleukin-10. Infect Immun 77:98–107

    PubMed Central  PubMed  Google Scholar 

  • Panda AK, Ravindran B, Das BK (2013) Rheumatoid arthritis patients are free of filarial infection in an area where filariasis is endemic: comment on the article by Pineda et al. Arthritis Rheum 65:1402–3

    PubMed  Google Scholar 

  • Park SK, Cho MK, Park HK et al (2009) Macrophage migration inhibitory factor homologs of anisakis simplex suppress Th2 response in allergic airway inflammation model via CD4 + CD25 + Foxp3+ T cell recruitment. J Immunol 182:6907–14

    CAS  PubMed  Google Scholar 

  • Park HK, Cho MK, Choi SH, Kim YS, Yu HS (2011) Trichinella spiralis: infection reduces airway allergic inflammation in mice. Exp Parasitol 127:539–44

    CAS  PubMed  Google Scholar 

  • Peres RS, Chiuso-Minicucci F, da Rosa LC, Domingues A, Zorzella-Pezavento SF, França TG et al (2013) Previous contact with Strongyloides venezuelensis contributed to prevent insulitis in MLD-STZ diabetes. Exp Parasitol 134:183–9

    PubMed  Google Scholar 

  • Pineda MA, McGrath MA, Smith PC, Al-Riyami L, Rzepecka J, Gracie JA et al (2012) The parasitic helminth product ES-62 suppresses pathogenesis in collagen-induced arthritis by targeting the interleukin-17-producing cellular network at multiple sites. Arthritis Rheum 64:3168–78

    CAS  PubMed  Google Scholar 

  • Pinto LA, Pitrez PM, Fontoura GR, Machado DC, Jones MH, Graeff-Teixeira C et al (2004) Infection of BALB/c mice with Angiostrongylus costaricensis decreases pulmonary inflammatory response to ovalbumin. Parasite Immunol 26:151–5

    CAS  PubMed  Google Scholar 

  • Pinto LA, Dias AC, Rymer BL, Fernandes FF, Barbosa GL, Machado DC et al (2006) Effect of Angiostrongylus costaricensis extract on eosinophilic pulmonary response in BALB/c mice. Parasitol Res 98:295–8

    PubMed  Google Scholar 

  • Reardon C, Sanchez A, Hogaboam CM, McKay DM (2001) Tapeworm infection reduces epithelial ion transport abnormalities in murine dextran sulfate sodium-induced colitis. Infect Immun 69:4417–23

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reyes JL, Espinoza-Jiménez AF, González MI, Verdin L, Terrazas LI (2011) Taenia crassiceps infection abrogates experimental autoimmune encephalomyelitis. Cell Immunol 267:77–87

    CAS  PubMed  Google Scholar 

  • Rocha FA, Leite AK, Pompeu MM, Cunha TM, Verri WA Jr, Soares FM et al (2008) Protective effect of an extract from Ascaris suum in experimental arthritis models. Infect Immun 76:2736–45

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ruyssers NE, De Winter BY, De Man JG, Loukas A, Pearson MS, Weinstock JV et al (2009) Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis 15:491–500

    PubMed  Google Scholar 

  • Ruyssers NE, De Winter BY, De Man JG, Ruyssers ND, Van Gils AJ, Loukas A et al (2010) Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice. World J Gastroenterol 16:703–12

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rzepecka J, Donskow-Schmelter K, Doligalska M (2007) Heligmosomoides polygyrus infection down-regulates eotaxin concentration and CCR3 expression on lung eosinophils in murine allergic pulmonary inflammation. Parasite Immunol 29:405–13

    CAS  PubMed  Google Scholar 

  • Rzepecka J, Siebeke I, Coltherd JC, Kean DE, Steiger CN, Al-Riyami L et al (2013) The helminth product, ES-62, protects against airway inflammation by resetting the Th cell phenotype. Int J Parasitol 43:211–23

    CAS  PubMed Central  PubMed  Google Scholar 

  • Salinas-Carmona MC, de la Cruz-Galicia G, Pérez-Rivera I, Solís-Soto JM, Segoviano-Ramirez JC, Vázquez AV, Garza MA (2009) Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus aureus and ameliorated by Nippostrongylus brasiliensis infections. Autoimmunity 42:25–32

    CAS  PubMed  Google Scholar 

  • Sandborn WJ, Elliott DE, Weinstock J, Summers RW, Landry-Wheeler A, Silver N et al (2013) Randomised clinical trial: the safety and tolerability of Trichuris suis ova in patients with Crohn’s disease. Aliment Pharmacol Ther 38:255–63

    CAS  PubMed  Google Scholar 

  • Saunders KA, Raine T, Cooke A, Lawrence CE (2007) Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun 75:397–407

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schnoeller C, Rausch S, Pillai S, Avagyan A, Wittig BM, Loddenkemper C et al (2008) A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages. J Immunol 180:4265–72

    CAS  PubMed  Google Scholar 

  • Setiawan T, Metwali A, Blum AM, Ince MN, Urban JF Jr, Elliott DE et al (2007) Heligmosomoides polygyrus promotes regulatory T-cell cytokine production in the murine normal distal intestine. Infect Immun 75:4655–63

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sewell D, Qing Z, Reinke E, Elliot D, Weinstock J, Sandor M et al (2003) Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. Int Immunol 15:59–69

    CAS  PubMed  Google Scholar 

  • Shi M, Wang A, Prescott D, Waterhouse CC, Zhang S, McDougall JJ et al (2011) Infection with an intestinal helminth parasite reduces Freund’s complete adjuvant-induced monoarthritis in mice. Arthritis Rheum 63:434–44

    CAS  PubMed  Google Scholar 

  • Smith P, Mangan NE, Walsh CM, Fallon RE, McKenzie AN, van Rooijen N et al (2007) Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol 178:4557–66

    CAS  PubMed  Google Scholar 

  • Sofronic-Milosavljevic LJ, Radovic I, Ilic N, Majstorovic I, Cvetkovic J, Gruden-Movsesijan A (2013) Application of dendritic cells stimulated with Trichinella spiralis excretory-secretory antigens alleviates experimental autoimmune encephalomyelitis. Med Microbiol Immunol 202:239–49

    CAS  PubMed  Google Scholar 

  • Song X, Shen J, Wen H, Zhong Z, Luo Q, Chu D et al (2011) Impact of Schistosoma japonicum infection on collagen-induced arthritis in DBA/1 mice: a murine model of human rheumatoid arthritis. PLoS One 6:e23453

    CAS  PubMed Central  PubMed  Google Scholar 

  • Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV (2005a) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128:825–32

    PubMed  Google Scholar 

  • Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV (2005b) Trichuris suis therapy in Crohn’s disease. Gut 54:87–90

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sun X, Liu YH, Lv ZY, Yang LL, Hu SM, Zheng HQ et al (2010) rSj16, a recombinant protein of Schistosoma japonicum-derived molecule, reduces severity of the complete Freund’s adjuvant-induced adjuvant arthritis in rats’ model. Parasite Immunol 32:739–48

    CAS  PubMed  Google Scholar 

  • Sutton TL, Zhao A, Madden KB, Elfrey JE, Tuft BA, Sullivan CA et al (2008) Anti-Inflammatory mechanisms of enteric Heligmosomoides polygyrus infection against trinitrobenzene sulfonic acid-induced colitis in a murine model. Infect Immun 76:4772–82

    CAS  PubMed Central  PubMed  Google Scholar 

  • Trujillo-Vargas CM, Werner-Klein M, Wohlleben G, Polte T, Hansen G, Ehlers S et al (2007) Helminth-derived products inhibit the development of allergic responses in mice. Am J Respir Crit Care Med 175:336–44

    CAS  PubMed  Google Scholar 

  • van der Vlugt LE, Labuda LA, Ozir-Fazalalikhan A, Lievers E, Gloudemans AK, Liu KY, Barr TA, Sparwasser T, Boon L, Ngoa UA, Feugap EN, Adegnika AA, Kremsner PG, Gray D, Yazdanbakhsh M, Smits HH (2012) Schistosomes induce regulatory features in human and mouse CD1d(hi) B cells: inhibition of allergic inflammation by IL-10 and regulatory T cells. PLoS One 7(2):e30883

    PubMed Central  PubMed  Google Scholar 

  • van der Werff SD, Twisk JW, Wördemann M, Ponce MC, Díaz RJ, Núñez FA et al (2013) Deworming is not a risk factor for the development of atopic diseases: a longitudinal study in Cuban school children. Clin Exp Allergy 43:665–71

    PubMed  Google Scholar 

  • Walsh KP, Brady MT, Finlay CM, Boon L, Mills KH (2009) Infection with a helminth parasite attenuates autoimmunity through TGF-beta-mediated suppression of Th17 and Th1 responses. J Immunol 183:1577–86

    CAS  PubMed  Google Scholar 

  • Wang CC, Nolan TJ, Schad GA, Abraham D (2001) Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin. Clin Exp Allergy 31:495–503

    CAS  PubMed  Google Scholar 

  • Weinstock JV (2012) Autoimmunity: The worm returns. Nature 491:183–5

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson MS, Taylor MD, O’Gorman MT, Balic A, Barr TA, Filbey K et al (2010) Helminth-induced CD19 + CD23hi B cells modulate experimental allergic and autoimmune inflammation. Eur J Immunol 40:1682–96

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wohlleben G, Trujillo C, Muller J, Ritze Y, Grunewald S, Tatsch U et al (2004) Helminth infection modulates the development of allergen-induced airway inflammation. Int Immunol 16:585–596

    CAS  PubMed  Google Scholar 

  • Wu Z, Nagano I, Asano K, Takahashi Y (2010) Infection of non-encapsulated species of Trichinella ameliorates experimental autoimmune encephalomyelitis involving suppression of Th17 and Th1 response. Parasitol Res 107:1173–88

    PubMed  Google Scholar 

  • Xia CM, Zhao Y, Jiang L, Jiang J, Zhang SC (2011) Schistosoma japonicum ova maintains epithelial barrier function during experimental colitis. World J Gastroenterol 17:4810–6

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang J, Zhao J, Yang Y, Zhang L, Yang X, Zhu X et al (2007) Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma. Immunology 120:8–18

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zaccone P, Fehérvári Z, Jones FM, Sidobre S, Kronenberg M, Dunne DW et al (2003) Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur J Immunol 33:1439–49

    CAS  PubMed  Google Scholar 

  • Zaccone P, Burton O, Miller N, Jones FM, Dunne DW, Cooke A (2009) Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice. Eur J Immunol 39:1098–107

    CAS  PubMed  Google Scholar 

  • Zaccone P, Burton OT, Gibbs S, Miller N, Jones FM, Dunne DW et al (2010) Immune modulation by Schistosoma mansoni antigens in NOD mice: effects on both innate and adaptive immune systems. J Biomed Biotechnol 2010:795210

    PubMed Central  PubMed  Google Scholar 

  • Zaccone P, Burton OT, Gibbs SE, Miller N, Jones FM, Schramm G et al (2011) The S. mansoni glycoprotein ω-1 induces Foxp3 expression in NOD mouse CD4+ T cells. Eur J Immunol 41:2709–18

    CAS  PubMed  Google Scholar 

  • Zhao Y, Zhang S, Jiang L, Jiang J, Liu H (2009) Preventive effects of Schistosoma japonicum ova on trinitrobenzenesulfonic acid-induced colitis and bacterial translocation in mice. J Gastroenterol Hepatol 24:1775–80

    PubMed  Google Scholar 

  • Zheng X, Hu X, Zhou G, Lu Z, Qiu W, Bao J et al (2008) Soluble egg antigen from Schistosoma japonicum modulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response. J Neuroimmunol 194:107–14

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William Harnett .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Wien

About this chapter

Cite this chapter

Rzepecka, J., Harnett, W. (2014). Can the Study of Helminths Be Fruitful for Human Diseases?. In: Bruschi, F. (eds) Helminth Infections and their Impact on Global Public Health. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1782-8_16

Download citation

Publish with us

Policies and ethics