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Do We Need Worms to Promote Immune Health?

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Abstract

Many immune-mediated diseases like inflammatory bowel disease, multiple sclerosis, type 1 diabetes, asthma, and food allergy appeared to have increased in frequency in developed countries in the latter part of the twentieth century. Reports from less developed countries suggest that the “epidemic” of immune-mediated diseases now is spreading into these regions as well. The “hygiene hypothesis” was developed to partly explain this phenomenon. It has been proposed that modern-day sanitary living has altered our exposure to organisms that provided protection from these diseases in the past. Alternations in the composition of our intestinal flora and fauna could play a role. Helminths are a group of worm-like parasitic organisms that have adapted to live in various regions of their hosts. Epidemiological and some clinical data suggest that these organisms can protect people from developing immune-mediated diseases. Animal experimentation has shown that helminths stimulate the production of regulatory cytokines, activate regulatory T cells, and induce regulatory dendritic cells and macrophages. This could be the mechanism by which they protect the host from these diseases. Early clinical studies also suggest that helminths may prove useful for treating immunological diseases. More sophisticated clinical studies are underway, testing live helminth agents as therapeutic agents. Also, a strong effort is ongoing to discover the agents produced by helminths that modulate host immune responses with an eye on developing new, highly effective immune modulatory therapeutic agent.

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Abbreviations

CLEC:

C-type lectin-like domain-containing

CTLR:

C-type lectin receptors

DCs:

Dendritic cells

Hpb :

Heligmosomoides polygyrus bakeri

IBD:

Inflammatory bowel disease

Tregs:

Regulatory T cells

Tlr:

Toll-like receptors

References

  1. Poinar G Jr, Boucot AJ (2006) Evidence of intestinal parasites of dinosaurs. Parasitol 133(Pt 2):245–9

    Article  Google Scholar 

  2. Stoll NR (1947) This wormy world. J Parasitol 33:1–18

    Article  CAS  PubMed  Google Scholar 

  3. de Silva NR, Brooker S, Hotez PJ, Montresor A, Engels D, Savioli L (2003) Soil-transmitted helminth infections: updating the global picture. Trends Parasitol 19:547–551

    Article  PubMed  Google Scholar 

  4. Weinstock JV, Summers R, Elliott DE (2004) Helminths and harmony. Gut 53:7–9

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Ascherio A, Munger KL, Lunemann JD (2012) The initiation and prevention of multiple sclerosis. [Review]. Nat Rev Neurol 8:602–612

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Melcon MO, Melcon CM, Bartoloni L, Cristiano E, Duran JC, Grzesiuk AK, Fragoso YD, Brooks JB, Diaz V, Romero Garcia KM, Cabrera Gomez JA, Abad P, Islas MA, Gracia F, de Diaz Bedoya VF, Ruiz ME, Hackembruch JH, Oehninger C, Ketzoian CN, Soto A, Grupo Colaborativo Multicentrico para el Estudio de la Esclerosis Multiple en America Latina (2013) Towards establishing MS prevalence in Latin America and the Caribbean. Mult Scler 19:145–152

    Article  CAS  PubMed  Google Scholar 

  7. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterol 142:46–54

    Article  Google Scholar 

  8. Egro FM (2013) Why is type 1 diabetes increasing? J Mol Endocrinol 51:R1–13

    Article  CAS  PubMed  Google Scholar 

  9. Eder W, Ege MJ, von Mutius E (2006) The asthma epidemic. N Engl J Med 355:2226–2235

    Article  CAS  PubMed  Google Scholar 

  10. Sicherer SH, Sampson HA (2014) Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J All Clin Immunol 133:291–307

    Article  CAS  Google Scholar 

  11. Sonnenberg A, McCarty DJ, Jacobsen SJ (1991) Geographic variation of inflammatory bowel disease within the United States. Gastroenterol 100:143–149

    CAS  Google Scholar 

  12. Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, van Blankenstein M (1996) Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD). Gut 39:690–697

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Koch-Henriksen N, Sorensen PS (2011) Why does the north–south gradient of incidence of multiple sclerosis seem to have disappeared on the northern hemisphere? J Neurol Sci 311:58–63

    Article  PubMed  Google Scholar 

  14. Carr I, Mayberry JF (1999) The effects of migration on ulcerative colitis: a three-year prospective study among Europeans and first- and second- generation South Asians in Leicester (1991–1994). Am J Gastroenterol 94:2918–2922

    CAS  PubMed  Google Scholar 

  15. Jayanthi V, Probert CS, Pinder D, Wicks AC, Mayberry JF (1992) Epidemiology of Crohn’s disease in Indian migrants and the indigenous population in Leicestershire. Q J Med 82:125–138

    CAS  PubMed  Google Scholar 

  16. Probert CS, Jayanthi V, Hughes AO, Thompson JR, Wicks AC, Mayberry JF (1993) Prevalence and family risk of ulcerative colitis and Crohn’s disease: an epidemiological study among Europeans and south Asians in Leicestershire. Gut 34:1547–1551

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV (2010) Environmental factors and their timing in adult-onset multiple sclerosis. Nat Rev Neurol 6:156–166

    Article  PubMed  Google Scholar 

  18. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. [Review]. Gastroenterol 142:46–54

    Article  Google Scholar 

  19. Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Eng J Med 347(12):911–20

    Article  Google Scholar 

  20. Yazdanbakhsh M, Kremsner PG, van Ree R (2002) Allergy, parasites, and the hygiene hypothesis. Science 296:490–494

    Article  CAS  PubMed  Google Scholar 

  21. Elliott DE, Urban JF Jr, Argo CK, Weinstock JV (2000) Does the failure to acquire helminthic parasites predispose to Crohn’s disease? FASEB J 14:1848–1855

    Article  CAS  PubMed  Google Scholar 

  22. Correale J, Farez MF (2011) The impact of environmental infections (parasites) on MS activity. Mult Scler 17:1162–1169

    Article  CAS  PubMed  Google Scholar 

  23. 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 34:923–930

    Article  CAS  PubMed  Google Scholar 

  24. van den Biggelaar AH, Rodrigues LC, van Ree R, van der Zee JS, Hoeksma-Kruize YC, Souverijn JH, Missinou MA, Borrmann S, Kremsner PG, Yazdanbakhsh M (2004) Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren. J Inf Dis 189:892–900

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Correale J, Farez M (2009) Helminth antigens modulate immune responses in cells from multiple sclerosis patients through TLR2-dependent mechanisms. J Immunol 183(9):5999–6012

    Article  CAS  PubMed  Google Scholar 

  27. Fleming JO, Isaak A, Lee JE, Luzzio CC, Carrithers MD, Cook TD, Field AS, Boland J, Fabry Z (2011) Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study. Multiple Sclerosis J. 1–12

  28. Scrivener S, Yemaneberhan H, Zebenigus M, Tilahun D, Girma S, Ali S, McElroy P, Custovic A, Woodcock A, Pritchard D, Venn A, Britton J (2001) Independent effects of intestinal parasite infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case–control study. Lancet 358:1493–1499

    Article  CAS  PubMed  Google Scholar 

  29. Flohr C, Tuyen LN, Lewis S, Quinnell R, Minh TT, Liem HT, Campbell J, Pritchard D, Hien TT, Farrar J, Williams H, Britton J (2006) Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: a cross-sectional study. J All Clin Immunol 118(6):1305–11

    Article  Google Scholar 

  30. Buning J, Homann N, von Smolinski D, Borcherding F, Noack F, Stolte M, Kohl M, Lehnert H, Ludwig D (2008) Helminths as governors of inflammatory bowel disease. Gut 57:1182–1183

    Article  CAS  PubMed  Google Scholar 

  31. Broadhurst MJ, Leung JM, Kashyap V, McCune JM, Mahadevan U, McKerrow JH, Loke P (2010) IL-22+ CD4+ T cells are associated with therapeutic trichuris trichiura infection in an ulcerative colitis patient. Sci Trans Med 2:60ra88

    Article  CAS  Google Scholar 

  32. Pugazhendhi S, Sahu MK, Subramanian V, Pulimood A, Ramakrishna BS (2011) Environmental factors associated with Crohn’s disease in India. Indian J Gastroenterol 30:264–269

    Article  PubMed  Google Scholar 

  33. Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Riva S, Clerici M, Bresolin N, Sironi M (2009) Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. J Exp Med 206:1395–1408

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Bager P, Vinkel HA, 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

    Article  PubMed  Google Scholar 

  35. Amre DK, Lambrette P, Law L, Krupoves A, Chotard V, Costea F, Grimard G, Israel D, Mack D, Seidman EG (2006) Investigating the hygiene hypothesis as a risk factor in pediatric onset Crohn’s disease: a case–control study. Am J Gastroenterol 101:1005–1011

    Article  PubMed  Google Scholar 

  36. Weinstock JV, Elliott DE (2014) Helminth infections decrease host susceptibility to immune-mediated diseases. J Immunol 193:3239–3247

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Hang L, Setiawan T, Blum AM, Urban J, Stoyanoff K, Arihiro S, Reinecker HC, Weinstock JV (2010) Heligmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity. J Immunol 185:3184–3189

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Dragicevic A, Dzopalic T, Vasilijic S, Vucevic D, Tomic S, Bozic B, Colic M (2012) Signaling through Toll-like receptor 3 and Dectin-1 potentiates the capability of human monocyte-derived dendritic cells to promote T-helper 1 and T-helper 17 immune responses. Cytotherapy 14:598–607

    Article  CAS  PubMed  Google Scholar 

  39. Dzopalic T, Rajkovic I, Dragicevic A, Colic M (2012) The response of human dendritic cells to co-ligation of pattern-recognition receptors. Immunol Res 52:20–33

    Article  CAS  PubMed  Google Scholar 

  40. van Ampting MT, Loonen LM, Schonewille AJ, Konings I, Vink C, Iovanna J, Chamaillard M, Dekker J, van der Meer R, Wells JM, Bovee-Oudenhoven IM (2012) Intestinally secreted C-type lectin Reg3b attenuates salmonellosis but not listeriosis in mice. Inf Immun 80:1115–1120

    Article  Google Scholar 

  41. Vaishnava S, Yamamoto M, Severson KM, Ruhn KA, Yu X, Koren O, Ley R, Wakeland EK, Hooper LV (2011) The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science 334:255–258

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV (2005) Trichuris suis therapy in Crohn’s disease. Gut 54(1):87–90

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV (2005) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterol 128(4):825–32

    Article  Google Scholar 

  44. Summers RW, Elliott DE, Weinstock JV (2005) Is there a role for helminths in the therapy of inflammatory bowel disease? Nat Clin Practice Gastroenterol Hep 2:62–63

    Article  Google Scholar 

  45. Croese J, O’Neil J, Masson J, Cooke S, Melrose W, Pritchard D, Speare R (2006) A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors. Gut 55:136–137

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Correspondence to Joel V. Weinstock.

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Weinstock, J.V. Do We Need Worms to Promote Immune Health?. Clinic Rev Allerg Immunol 49, 227–231 (2015). https://doi.org/10.1007/s12016-014-8458-3

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  • DOI: https://doi.org/10.1007/s12016-014-8458-3

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