Unraveling the hygiene hypothesis of helminthes and autoimmunity: Origins, pathophysiology, and clinical applications

BMC Medicine

Volumn 13, Issue 1, 2015, Pages

  Versini, Mathilde ^a,b   Jeandel, Pierre Yves ^b   Bashi, Tomer ^a   Bizzaro, Giorgia ^a   Blank, Miri ^a   Shoenfeld, Yehuda ^a,c  

^a SHEBA MEDICAL CENTER   (Israel)

^b CENTRE HOSPITALIER UNIVERSITAIRE DE NICE   (France)

^c TEL AVIV UNIVERSITY   (Israel)

Author keywords

Allergy; Autoantibodies; Autoimmune disease; Autoimmunity; Helminthes; Hygiene hypothesis; Infection; Parasite; T regulatory cells; Th1

Indexed keywords

ALLERGIC DISEASE; ARTICLE; AUTOIMMUNITY; B LYMPHOCYTE; CELIAC DISEASE; DENDRITIC CELL; DISEASE CARRIER; EVOLUTION; FOOD PROCESSING; GRAVES DISEASE; HELMINTH; HUMAN; HYGIENE HYPOTHESIS; IMMUNE RESPONSE; IMMUNOMODULATION; INFLAMMATORY BOWEL DISEASE; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; MICROBIOME; MICROFLORA; MIGRATION; MULTIPLE SCLEROSIS; NONHUMAN; PATHOPHYSIOLOGY; REGULATORY MECHANISM; RHEUMATOID ARTHRITIS; SPACE; SYSTEMIC LUPUS ERYTHEMATOSUS; TH1 CELL; TH2 CELL; THERAPY WITH HELMINTHS; URBANIZATION; ANIMAL; AUTOIMMUNE DISEASE; HELMINTHIASIS; IMMUNOLOGY;

HELMINTH ANTIBODY; PARASITE ANTIGEN;

ANIMALS; ANTIBODIES, HELMINTH; ANTIGENS, HELMINTH; AUTOIMMUNE DISEASES; AUTOIMMUNITY; HELMINTHIASIS; HUMANS; HYGIENE HYPOTHESIS;

EID: 84927520409     PISSN: None     EISSN: 17417015     Source Type: Journal    
DOI: 10.1186/s12916-015-0306-7     Document Type: Article

References (188)

1. Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med. 2006;23:2226-35.
2. Bieber T. Atopic dermatitis. N Engl J Med. 2008;358:1483-94.
3. Patterson CC, Dahlquist GG, Gyürüs E, Green A, Soltész G. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet. 2009;373:2027-33.
4. Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140:1785-94.
5. Moroni L, Bianchi I, Lleo A. Geoepidemiology, gender and autoimmune disease. Autoimmun Rev. 2012;11:A386-92.
6. World Health Organization. Atlas: Multiple sclerosis resources in the world 2008. Geneva: WHO; 2008.
7. Costenbader KH, Gay S, Alarcón-Riquelme ME, Iaccarino L, Doria A. Genes, epigenetic regulation and environmental factors: which is the most relevant in developing autoimmune diseases? Autoimmun Rev. 2012;11:604-9.
8. Colafrancesco S, Agmon-Levin N, Perricone C, Shoenfeld Y. Unraveling the soul of autoimmune diseases: pathogenesis, diagnosis and treatment adding dowels to the puzzle. Immunol Res. 2013;56:200-5.
9. Antico A, Tampoia M, Tozzoli R, Bizzaro N. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 2012;12:127-36.
10. Arnson Y, Shoenfeld Y, Amital H. Effects of tobacco smoke on immunity, inflammation and autoimmunity. J Autoimmun. 2010;34:J258-65.
11. Farhat SCL, Silva CA, Orione MAM, Campos LMA, Sallum AME, Braga ALF. Air pollution in autoimmune rheumatic diseases: a review. Autoimmun Rev. 2011;11:14-21.
12. Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical and diagnostic aspects. J Autoimmun. 2013;47:1-16.
13. Versini M, Jeandel P-Y, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev. 2014;13:981-1000.
14. Bogdanos DP, Smyk DS, Invernizzi P, Rigopoulou EI, Blank M, Pouria S, et al. Infectome: a platform to trace infectious triggers of autoimmunity. Autoimmun Rev. 2013;12:726-40.
15. Okada H, Kuhn C, Feillet H, Bach J-F. The "hygiene hypothesis" for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010;160:1-9.
16. Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299:1259-60.
17. Brown EM, Arrieta M-C, Finlay BB. A fresh look at the hygiene hypothesis: how intestinal microbial exposure drives immune effector responses in atopic disease. Semin Immunol. 2013;25:378-87.
18. Bendiks M, Kopp MV. The relationship between advances in understanding the microbiome and the maturing hygiene hypothesis. Curr Allergy Asthma Rep. 2013;13:487-94.
19. Parker W. The "hygiene hypothesis" for allergic disease is a misnomer. BMJ. 2014;348:g5267.
20. Bach J-F. Infections and autoimmune diseases. J Autoimmun. 2005;25:74-80.
21. Saeki Y, Ishihara K. Infection-immunity liaison: pathogen-driven autoimmune-mimicry (PDAIM). Autoimmun Rev. 2014;13:1064-9.
22. Zandman-Goddard G, Shoenfeld Y. Parasitic infection and autoimmunity. Lupus. 2009;18:1144-8.
23. Elliott DE, Weinstock JV. Helminth-host immunological interactions: prevention and control of immune-mediated diseases. Ann N Y Acad Sci. 2012;1247:83-96.
24. Rook GAW. Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42:5-15.
25. Greenwood BM. Autoimmune disease and parasitic infections in Nigerians. Lancet. 1968;2:380-2.
26. Greenwood BM, Herrick EM, Voller A. Suppression of autoimmune disease in NZB and (NZB x NZW) F1 hybrid mice by infection with malaria. Nature. 1970;226:266-7.
27. Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med. 2000;343:538-43.
28. Benn CS, Melbye M, Wohlfahrt J, Björkstén B, Aaby P. Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life. BMJ. 2004;328:1223.
29. Goldberg S, Israeli E, Schwartz S, Shochat T, Izbicki G, Toker-Maimon O, et al. Asthma prevalence, family size, and birth order. Chest. 2007;131:1747-52.
30. Nicolaou NC, Simpson A, Lowe LA, Murray CS, Woodcock A, Custovic A. Day-care attendance, position in sibship, and early childhood wheezing: a population-based birth cohort study. J Allergy Clin Immunol. 2008;122:500-6.
31. Strachan DP, Aït-Khaled N, Foliaki S, Mallol J, Odhiambo J, Pearce N, et al. Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood. Clin Exp Allergy. 2015;45:126-36.
32. Pelucchi C, Galeone C, Bach J-F, La Vecchia C, Chatenoud L. Pet exposure and risk of atopic dermatitis at the pediatric age: a meta-analysis of birth cohort studies. J Allergy Clin Immunol. 2013;132:616-22.
33. Nowak D, Heinrich J, Jörres R, Wassmer G, Berger J, Beck E, et al. Prevalence of respiratory symptoms, bronchial hyperresponsiveness and atopy among adults: west and east Germany. Eur Respir J. 1996;9:2541-52.
34. Heinrich J, Hoelscher B, Frye C, Meyer I, Wjst M, Wichmann HE. Trends in prevalence of atopic diseases and allergic sensitization in children in Eastern Germany. Eur Respir J. 2002;19:1040-6.
35. Crane J, Wickens K. Antibiotics and asthma: a tricky tributary of the hygiene hypothesis. Lancet Respir Med. 2014;2:595-7.
36. Alm B, Goksör E, Pettersson R, Möllborg P, Erdes L, Loid P, et al. Antibiotics in the first week of life is a risk factor for allergic rhinitis at school age. Pediatr Allergy Immunol. 2014;25:468-72.
37. Wennergren G, Ekerljung L, Alm B, Eriksson J, Lötvall J, Lundbäck B. Asthma in late adolescence-farm childhood is protective and the prevalence increase has levelled off. Pediatr Allergy Immunol. 2010;21:806-13.
38. Solis Soto MT, Patiño A, Nowak D, Radon K. Prevalence of asthma, rhinitis and eczema symptoms in rural and urban school-aged children from Oropeza Province, Bolivia: a cross-sectional study. BMC Pulm Med. 2014;14:40.
39. Cooper PJ, Chico ME, Rodrigues LC, Ordonez M, Strachan D, Griffin GE, et al. Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics. J Allergy Clin Immunol. 2003;111:995-1000.
40. Van den Biggelaar AHJ, Rodrigues LC, van Ree R, van der Zee JS, Hoeksma-Kruize YCM, Souverijn JHM, et al. Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren. J Infect Dis. 2004;189:892-900.
41. Araujo MI, Lopes AA, Medeiros M, Cruz AA, Sousa-Atta L, Solé D, et al. Inverse association between skin response to aeroallergens and Schistosoma mansoni infection. Int Arch Allergy Immunol. 2000;123:145-8.
42. Lynch NR, Hagel I, Perez M, Di Prisco MC, Lopez R, Alvarez N. Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum. J Allergy Clin Immunol. 1993;92:404-11.
43. Flohr C, Tuyen LN, Lewis S, Quinnell R, Minh TT, Liem HT, et al. Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: a cross-sectional study. J Allergy Clin Immunol. 2006;118:1305-11.
44. Conradi S, Malzahn U, Schröter F, Paul F, Quill S, Spruth E, et al. Environmental factors in early childhood are associated with multiple sclerosis: a case-control study. BMC Neurol. 2011;11:123.
45. Hughes A-M, Lucas RM, McMichael AJ, Dwyer T, Pender MP, van der Mei I, et al. Early-life hygiene-related factors affect risk of central nervous system demyelination and asthma differentially. Clin Exp Immunol. 2013;172:466-74.
46. Bitti PP, Murgia BS, Ticca A, Ferrai R, Musu L, Piras ML, et al. Association between the ancestral haplotype HLA A30B18DR3 and multiple sclerosis in central Sardinia. Genet Epidemiol. 2001;20:271-83.
47. Sotgiu S, Pugliatti M, Sotgiu A, Sanna A, Rosati G. Does the "hygiene hypothesis" provide an explanation for the high prevalence of multiple sclerosis in Sardinia? Autoimmunity. 2003;36:257-60.
48. Sotgiu S, Sannella AR, Conti B, Arru G, Fois ML, Sanna A, et al. Multiple sclerosis and anti-Plasmodium falciparum innate immune response. J Neuroimmunol. 2007;185:201-7.
49. Sotgiu S, Angius A, Embry A, Rosati G, Musumeci S. Hygiene hypothesis: innate immunity, malaria and multiple sclerosis. Med Hypotheses. 2008;70:819-25.
50. Seiskari T, Kondrashova A, Viskari H, Kaila M, Haapala A-M, Aittoniemi J, et al. Allergic sensitization and microbial load-a comparison between Finland and Russian Karelia. Clin Exp Immunol. 2007;148:47-52.
51. Kondrashova A, Seiskari T, Ilonen J, Knip M, Hyöty H. The "Hygiene hypothesis" and the sharp gradient in the incidence of autoimmune and allergic diseases between Russian Karelia and Finland. APMIS. 2013;121:478-93.
52. Elliott DE, Urban JFJR, Argo CK, Weinstock JV. Does the failure to acquire helminthic parasites predispose to Crohn's disease? FASEB J. 2000;14:1848-55.
53. Fiasse R, Latinne D. Intestinal helminths: a clue explaining the low incidence of inflammatory bowel diseases in Subsaharan Africa? Potential benefits and hazards of helminth therapy. Acta Gastroenterol Belg. 2006;69:418-22.
54. Bodansky HJ, Staines A, Stephenson C, Haigh D, Cartwright R. Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population. BMJ. 1992;304:1020-2.
55. Staines A, Hanif S, Ahmed S, McKinney PA, Shera S, Bodansky HJ. Incidence of insulin dependent diabetes mellitus in Karachi. Pakistan Arch Dis Child. 1997;76:121-3.
56. Leibowitz U, Kahana E, Alter M. The changing frequency of multiple sclerosis in Israel. Arch Neurol. 1973;29:107-10.
57. Detels R, Brody JA, Edgar AH. Multiple sclerosis among American, Japanese and Chinese migrants to California and Washington. J Chronic Dis. 1972;25:3-10.
58. Symmons DP. Frequency of lupus in people of African origin. Lupus. 1995;4:176-8.
59. Panda AK, Ravindran B, Das BK. 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. 2013;65:1402-3.
60. Rook GAW, Raison CL, Lowry CA. Microbial "old friends", immunoregulation and socioeconomic status. Clin Exp Immunol. 2014;177:1-12.
61. Rook GAW. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: Darwinian medicine and the "hygiene" or "old friends" hypothesis. Clin Exp Immunol. 2010;160:70-9.
62. Dunder T, Tapiainen T, Pokka T, Uhari M. Infections in child day care centers and later development of asthma, allergic rhinitis, and atopic dermatitis: prospective follow-up survey 12 years after controlled randomized hygiene intervention. Arch Pediatr Adolesc Med. 2007;161:972-7.
63. Koloski N-A, Bret L, Radford-Smith G. Hygiene hypothesis in inflammatory bowel disease: a critical review of the literature. World J Gastroenterol. 2008;14:165-73.
64. Yoo J, Tcheurekdjian H, Lynch SV, Cabana M, Boushey HA. Microbial manipulation of immune function for asthma prevention: inferences from clinical trials. Proc Am Thorac Soc. 2007;4:277-82.
65. Ziegelbauer K, Speich B, Mäusezahl D, Bos R, Keiser J, Utzinger J. Effect of sanitation on soil-transmitted helminth infection: systematic review and meta-analysis. PLoS Med. 2012;9:e1001162.
66. Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J. Helminth infections: the great neglected tropical diseases. J Clin Invest. 2008;118:1311-21.
67. Murray CJL, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:1005-70.
68. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336:1268-73.
69. Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science. 2010;330:1768-73.
70. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157:121-41.
71. Karczewski J, Poniedzialek B, Adamski Z, Rzymski P. The effects of the microbiota on the host immune system. Autoimmunity. 2014;47:494-504.
72. Huang EY, Devkota S, Moscoso D, Chang EB, Leone VA. The role of diet in triggering human inflammatory disorders in the modern age. Microbes Infect. 2013;15:765-74.
73. Hanski I, von Hertzen L, Fyhrquist N, Koskinen K, Torppa K, Laatikainen T, et al. Environmental biodiversity, human microbiota, and allergy are interrelated. Proc Natl Acad Sci U S A. 2012;109:8334-9.
74. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222-7.
75. Azad MB, Konya T, Maughan H, Guttman DS, Field CJ, Sears MR, et al. Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity. Allergy Asthma Clin Immunol. 2013;9:15.
76. Penders J, Gerhold K, Thijs C, Zimmermann K, Wahn U, Lau S, et al. New insights into the hygiene hypothesis in allergic diseases: mediation of sibling and birth mode effects by the gut microbiota. Gut Microbes. 2014;5:239-44.
77. Maslowski KM, Mackay CR. Diet, gut microbiota and immune responses. Nat Immunol. 2011;12:5-9.
78. Vieira SM, Pagovich OE, Kriegel MA. Diet, microbiota and autoimmune diseases. Lupus. 2014;23:518-26.
79. Manzel A, Muller DN, Hafler DA, Kleinewietfeld M. Role of "Western Diet" in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014;14:404.
80. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107:14691-6.
81. Pérez-Cobas AE, Artacho A, Knecht H, Ferrús ML, Friedrichs A, Ott SJ, et al. Differential effects of antibiotic therapy on the structure and function of human gut microbiota. PLoS One. 2013;8:e80201.
82. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107:11971-5.
83. Kuo C-H, Kuo H-F, Huang C-H, Yang S-N, Lee M-S, Hung C-H. Early life exposure to antibiotics and the risk of childhood allergic diseases: an update from the perspective of the hygiene hypothesis. J Microbiol Immunol Infect. 2013;46:320-9.
84. Zeissig S, Blumberg RS. Life at the beginning: perturbation of the microbiota by antibiotics in early life and its role in health and disease. Nat Immunol. 2014;15:307-10.
85. Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell CR. A meta-analysis of the association between Caesarean section and childhood asthma. Clin Exp Allergy. 2008;38:629-33.
86. Cardwell CR, Stene LC, Joner G, Cinek O, Svensson J, Goldacre MJ, et al. Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies. Diabetologia. 2008;51:726-35.
87. Nielsen NM, Bager P, Stenager E, Pedersen BV, Koch-Henriksen N, Hjalgrim H, et al. Cesarean section and offspring's risk of multiple sclerosis: a Danish nationwide cohort study. Mult Scler. 2013;19:1473-7.
88. Decker E, Engelmann G, Findeisen A, Gerner P, Laass M, Ney D, et al. Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children. Pediatrics. 2010;125:e1433-40.
89. Mårild K, Stephansson O, Montgomery S, Murray JA, Ludvigsson JF. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology. 2012;142:39-45.
90. McSorley HJ, Maizels RM. Helminth infections and host immune regulation. Clin Microbiol Rev. 2012;25:585-608.
91. Weinstock JV. Autoimmunity: the worm returns. Nature. 2012;491:183-5.
92. Ben-Ami Shor D, Harel M, Eliakim R, Shoenfeld Y. The hygiene theory harnessing helminths and their ova to treat autoimmunity. Clin Rev Allergy Immunol. 2013;45:211-6.
93. Zaccone P, Cooke A. Vaccine against autoimmune disease: can helminths or their products provide a therapy? Curr Opin Immunol. 2013;25:418-23.
94. Maizels RM, McSorley HJ, Smyth DJ. Helminths in the hygiene hypothesis: sooner or later? Clin Exp Immunol. 2014;171:38-46.
95. Shor DB-A, Shoenfeld Y. Autoimmunity: will worms cure rheumatoid arthritis? Nat Rev Rheumatol. 2013;9:138-40.
96. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145-73.
97. Annunziato F, Romagnani S. Heterogeneity of human effector CD4+ T cells. Arthritis Res Ther. 2009;11:257.
98. Gause WC, Urban JF, Stadecker MJ. The immune response to parasitic helminths: insights from murine models. Trends Immunol. 2003;24:269-77.
99. Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8:345-50.
100. Singh RP, Hasan S, Sharma S, Nagra S, Yamaguchi DT, Wong D, et al. Th17 cells in inflammation and autoimmunity. Autoimmun Rev. 2014. Ahead of print.
101. Sakaguchi S. Regulatory T, cells: key controllers of immunologic self-tolerance. Cell. 2000;101:455-8.
102. Hawrylowicz CM, O'Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol. 2005;5:271-83.
103. Kim JM, Rasmussen JP, Rudensky AY. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol. 2007;8:191-7.
104. Sofronic-Milosavljevic L, Radovic I, Ilic N, Majstorovic I, Cvetkovic J, Gruden-Movsesijan A. Mechanisms of modulation of experimental autoimmune encephalomyelitis by chronic Trichinella spiralis infection in Dark Agouti rats. Parasite Immunol. 2010;32:450-9.
105. Elliott DE, Metwali A, Leung J, Setiawan T, Blum AM, Ince MN, et al. Colonization with Heligmosomoides polygyrus suppresses mucosal IL-17 production. J Immunol. 2008;181:2414-9.
106. Wu Z, Nagano I, Asano K, Takahashi Y. Infection of non-encapsulated species of Trichinella ameliorates experimental autoimmune encephalomyelitis involving suppression of Th17 and Th1 response. Parasitol Res. 2010;107:1173-88.
107. Osada Y, Shimizu S, Kumagai T, Yamada S, Kanazawa T. Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regulation of pro-inflammatory mediators. Int J Parasitol. 2009;39:457-64.
108. Pineda MA, McGrath MA, Smith PC, Al-Riyami L, Rzepecka J, Gracie JA, et al. 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. 2012;64:3168-78.
109. Saunders KA, Raine T, Cooke A, Lawrence CE. Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun. 2007;75:397-407.
110. Hübner MP, Stocker JT, Mitre E. 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. 2009;127:512-22.
111. Zaccone P, Fehérvári Z, Jones FM, Sidobre S, Kronenberg M, Dunne DW, et al. Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur J Immunol. 2003;33:1439-49.
112. Zaccone P, Burton O, Miller N, Jones FM, Dunne DW, Cooke A. Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice. Eur J Immunol. 2009;39:1098-107.
113. + T cells. Eur J Immunol. 2011;41:2709-18.
114. McInnes IB, Leung BP, Harnett M, Gracie JA, Liew FY, Harnett W. A novel therapeutic approach targeting articular inflammation using the filarial nematode-derived phosphorylcholine-containing glycoprotein ES-62. J Immunol. 2003;171:2127-33.
115. Hübner MP, Shi Y, Torrero MN, Mueller E, Larson D, Soloviova K, et al. Helminth protection against autoimmune diabetes in nonobese diabetic mice is independent of a type 2 immune shift and requires TGF-β. J Immunol. 2012;188:559-68.
116. Torres-Aguilar H, Blank M, Jara LJ, Shoenfeld Y. Tolerogenic dendritic cells in autoimmune diseases: crucial players in induction and prevention of autoimmunity. Autoimmun Rev. 2010;10:8-17.
117. Diebold SS. Determination of T-cell fate by dendritic cells. Immunol Cell Biol. 2008;86:389-97.
118. Pulendran B, Tang H, Manicassamy S. Programming dendritic cells to induce T(H)2 and tolerogenic responses. Nat Immunol. 2010;11:647-55.
119. White RR, Artavanis-Tsakonas K. How helminths use excretory secretory fractions to modulate dendritic cells. Virulence. 2012;3:668-77.
120. Everts B, Smits HH, Hokke CH, Yazdanbakhsh M. Helminths and dendritic cells: sensing and regulating via pattern recognition receptors, Th2 and Treg responses. Eur J Immunol. 2010;40:1525-37.
121. Sofronic-Milosavljevic LJ, Radovic I, Ilic N, Majstorovic I, Cvetkovic J, Gruden-Movsesijan A. Application of dendritic cells stimulated with Trichinella spiralis excretory-secretory antigens alleviates experimental autoimmune encephalomyelitis. Med Microbiol Immunol. 2013;202:239-49.
122. Hang L, Setiawan T, Blum AM, Urban J, Stoyanoff K, Arihiro S, et al. Heligmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity. J Immunol. 2010;185:3184-9.
123. Blum AM, Hang L, Setiawan T, Urban JP, Stoyanoff KM, Leung J, et al. Heligmosomoides polygyrus bakeri induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut T cell responses. J Immunol. 2012;189:2512-20.
124. Khan AR, Amu S, Saunders SP, Fallon PG. The generation of regulatory B cells by helminth parasites. Methods Mol Biol. 2014;1190:143-62.
125. Van der Vlugt LEPM, Zinsou JF, Ozir-Fazalalikhan A, Kremsner PG, Yazdanbakhsh M, Adegnika AA, et al. Interleukin 10 (IL-10)-producing CD1dhi regulatory B cells from schistosoma haematobium-infected individuals induce IL-10-positive T cells and suppress effector T-cell cytokines. J Infect Dis. 2014;210:1207-16.
126. Kalampokis I, Yoshizaki A, Tedder TF. IL-10-producing regulatory B cells (B10 cells) in autoimmune disease. Arthritis Res Ther. 2013;15:S1.
127. Yang M, Rui K, Wang S, Lu L. Regulatory B cells in autoimmune diseases. Cell Mol Immunol. 2013;10:122-32.
128. Rodgers DT, Pineda MA, McGrath MA, Al-Riyami L, Harnett W, Harnett MM. Protection against collagen-induced arthritis in mice afforded by the parasitic worm product, ES-62, is associated with restoration of the levels of interleukin-10-producing B cells and reduced plasma cell infiltration of the joints. Immunology. 2014;141:457-66.
129. Wilson MS, Taylor MD, O'Gorman MT, Balic A, Barr TA, Filbey K, et al. Helminth-induced CD19 + CD23hi B cells modulate experimental allergic and autoimmune inflammation. Eur J Immunol. 2010;40:1682-96.
130. Sattler S, Ling G-S, Xu D, Hussaarts L, Romaine A, Zhao H, et al. IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut. J Autoimmun. 2014;50:107-22.
131. Correale J, Farez M, Razzitte G. Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol. 2008;64:187-99.
132. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012;122:787-95.
133. Herbert DR, Hölscher C, Mohrs M, Arendse B, Schwegmann A, Radwanska M, et al. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity. 2004;20:623-35.
134. Taylor MD, Harris A, Nair MG, Maizels RM, Allen JE. F4/80+ alternatively activated macrophages control CD4+ T cell hyporesponsiveness at sites peripheral to filarial infection. J Immunol. 2006;176:6918-27.
135. Jang SW, Cho MK, Park MK, Kang SA, Na B-K, Ahn SC, et al. Parasitic helminth cystatin inhibits DSS-induced intestinal inflammation via IL-10(+)F4/80(+) macrophage recruitment. Korean J Parasitol. 2011;49:245-54.
136. Spits H, Cupedo T. Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu Rev Immunol. 2012;30:647-75.
137. Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cells-a proposal for uniform nomenclature. Nat Rev Immunol. 2013;13:145-9.
138. McSorley HJ, Blair NF, Smith KA, McKenzie AN, Maizels RM. Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy. Mucosal Immunol. 2014;7:1068-78.
139. Lee SC, Tang MS, Lim YAL, Choy SH, Kurtz ZD, Cox LM, et al. Helminth colonization is associated with increased diversity of the gut microbiota. PLoS Negl Trop Dis. 2014;8:e2880.
140. Walk ST, Blum AM, Ewing SA-S, Weinstock JV, Young VB. Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus. Inflamm Bowel Dis. 2010;16:1841-9.
141. Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y, et al. Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun. 2002;70:5931-7.
142. Elliott DE, Li J, Blum A, Metwali A, Qadir K, Urban JF, et al. Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol. 2003;284:G385-91.
143. Moreels TG, Nieuwendijk RJ, De Man JG, De Winter BY, Herman AG, Van Marck EA, et al. Concurrent infection with Schistosoma mansoni attenuates inflammation induced changes in colonic morphology, cytokine levels, and smooth muscle contractility of trinitrobenzene sulphonic acid induced colitis in rats. Gut. 2004;53:99-107.
144. Hunter MM, Wang A, Hirota CL, McKay DM. Neutralizing anti-IL-10 antibody blocks the protective effect of tapeworm infection in a murine model of chemically induced colitis. J Immunol. 2005;174:7368-75.
145. Smith P, Mangan NE, Walsh CM, Fallon RE, McKenzie ANJ, van Rooijen N, et al. Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol. 2007;178:4557-66.
146. Mo H, Liu W, Lei J, Cheng Y, Wang C, Li Y. Schistosoma japonicum eggs modulate the activity of CD4+ CD25+ Tregs and prevent development of colitis in mice. Exp Parasitol. 2007;116:385-9.
147. Motomura Y, Wang H, Deng Y, El-Sharkawy RT, Verdu EF, Khan WI. Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis. Clin Exp Immunol. 2009;155:88-95.
148. McKay DM. The immune response to and immunomodulation by Hymenolepis diminuta. Parasitology. 2010;137:385-94.
149. Summers RW, Elliott DE, Qadir K, Urban JF, Thompson R, Weinstock JV. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol. 2003;98:2034-41.
150. Summers RW, Elliott DE, Urban JF, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut. 2005;54:87-90.
151. Summers RW, Elliott DE, Urban JF, Thompson RA, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology. 2005;128:825-32.
152. Sandborn WJ, Elliott DE, Weinstock J, Summers RW, Landry-Wheeler A, Silver N, et al. Randomised clinical trial: the safety and tolerability of Trichuris suis ova in patients with Crohn's disease. Aliment Pharmacol Ther. 2013;38:255-63.
153. Lu L, Nanus M, Forman S. Coronado biosciences announces top-line results from its TRUST-I phase 2 clinical trial of TSO for the treatment of Crohn's disease. http://globenewswire.com/news-release/2013/10/14/580190/10052399/en/Coronado-Biosciences-Announces-Top-Line-Results-From-Its-TRUST-I-Phase-2-Clinical-Trial-of-TSO-for-the-Treatment-of-Crohn-s-Disease.html.
154. Wammes LJ, Mpairwe H, Elliott AM, Yazdanbakhsh M. Helminth therapy or elimination: epidemiological, immunological, and clinical considerations. Lancet Infect Dis. 2014;14:1150-62.
155. Croese J, O'Neil J, Masson J, Cooke S, Melrose W, Pritchard D, et al. A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors. Gut. 2006;55:136-7.
156. Mortimer K, Brown A, Feary J, Jagger C, Lewis S, Antoniak M, et al. Dose-ranging study for trials of therapeutic infection with Necator americanus in humans. Am J Trop Med Hyg. 2006;75:914-20.
157. Kuijk LM, Klaver EJ, Kooij G, van der Pol SMA, Heijnen P, Bruijns SCM, et al. Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation. Mol Immunol. 2012;51:210-8.
158. La Flamme AC, Ruddenklau K, Bäckström BT. Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immun. 2003;71:4996-5004.
159. Reyes JL, Espinoza-Jiménez AF, González MI, Verdin L, Terrazas LI. Taenia crassiceps infection abrogates experimental autoimmune encephalomyelitis. Cell Immunol. 2011;267:77-87.
160. Sewell D, Qing Z, Reinke E, Elliot D, Weinstock J, Sandor M, et al. Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. Int Immunol. 2003;15:59-69.
161. Walsh KP, Brady MT, Finlay CM, Boon L, Mills KHG. Infection with a helminth parasite attenuates autoimmunity through TGF-beta-mediated suppression of Th17 and Th1 responses. J Immunol. 2009;183:1577-86.
162. Zhu B, Trikudanathan S, Zozulya AL, Sandoval-Garcia C, Kennedy JK, Atochina O, et al. Immune modulation by Lacto-N-fucopentaose III in experimental autoimmune encephalomyelitis. Clin Immunol. 2012;142:351-61.
163. Gruden-Movsesijan A, Ilic N, Mostarica-Stojkovic M, Stosic-Grujicic S, Milic M, Sofronic-Milosavljevic L. Trichinella spiralis: modulation of experimental autoimmune encephalomyelitis in DA rats. Exp Parasitol. 2008;118:641-7.
164. Zheng X, Hu X, Zhou G, Lu Z, Qiu W, Bao J, et al. Soluble egg antigen from Schistosoma japonicum modulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response. J Neuroimmunol. 2008;194:107-14.
165. Correale J, Farez M. Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol. 2007;61:97-108.
166. Correale J, Farez MF. The impact of parasite infections on the course of multiple sclerosis. J Neuroimmunol. 2011;233:6-11.
167. Fleming JO, Isaak A, Lee JE, Luzzio CC, Carrithers MD, Cook TD, et al. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study. Mult Scler. 2011;17:743-54.
168. Fleming JO. Helminth therapy and multiple sclerosis. Int J Parasitol. 2013;43:259-74.
169. Pineda MA, Al-Riyami L, Harnett W, Harnett M. Themed issue 2014: lessons from helminth infections: ES-62 highlights new interventional approaches in rheumatoid arthritis. Clin Exp Immunol. 2014;177:13-23.
170. Harnett W, Worms MJ, Kapil A, Grainger M, Parkhouse RM. Origin, kinetics of circulation and fate in vivo of the major excretory-secretory product of Acanthocheilonema viteae. Parasitology. 1989;99:229-39.
171. Harnett MM, Kean DE, Boitelle A, McGuiness S, Thalhamer T, Steiger CN, et al. The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis. Ann Rheum Dis. 2008;67:518-23.
172. Pineda MA, Rodgers DT, Al-Riyami L, Harnett W, Harnett MM. ES-62 protects against collagen-induced arthritis by resetting Interleukin-22 toward resolution of inflammation in the joints. Arthritis Rheumatol (Hoboken, NJ). 2014;66:1492-503.
173. Al-Riyami L, Pineda MA, Rzepecka J, Huggan JK, Khalaf AI, Suckling CJ, et al. Designing anti-inflammatory drugs from parasitic worms: a synthetic small molecule analogue of the Acanthocheilonema viteae product ES-62 prevents development of collagen-induced arthritis. J Med Chem. 2013;56:9982-10002.
174. Shi M, Wang A, Prescott D, Waterhouse CCM, Zhang S, McDougall JJ, et al. Infection with an intestinal helminth parasite reduces Freund's complete adjuvant-induced monoarthritis in mice. Arthritis Rheum. 2011;63:434-44.
175. Carranza F, Falcón CR, Nuñez N, Knubel C, Correa SG, Bianco I, et al. Helminth antigens enable CpG-activated dendritic cells to inhibit the symptoms of collagen-induced arthritis through Foxp3+ regulatory T cells. PLoS One. 2012;7:e40356.
176. Song X, Shen J, Wen H, Zhong Z, Luo Q, Chu D, et al. Impact of Schistosoma japonicum infection on collagen-induced arthritis in DBA/1 mice: a murine model of human rheumatoid arthritis. PLoS One. 2011;6:e23453.
177. Salinas-Carmona MC, de la Cruz-Galicia G, Pérez-Rivera I, Solís-Soto JM, Segoviano-Ramirez JC, Vázquez AV, et al. Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus aureus and ameliorated by Nippostrongylus brasiliensis infections. Autoimmunity. 2009;42:25-32.
178. Cooke A, Tonks P, Jones FM, O'Shea H, Hutchings P, Fulford AJ, et al. Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol. 1999;21:169-76.
179. Zaccone P, Burton OT, Gibbs S, Miller N, Jones FM, Dunne DW, et al. Immune modulation by Schistosoma mansoni antigens in NOD mice: effects on both innate and adaptive immune systems. J Biomed Biotechnol. 2010;2010:795210.
180. Liu Q, Sundar K, Mishra PK, Mousavi G, Liu Z, Gaydo A, et al. Helminth infection can reduce insulitis and type 1 diabetes through CD25- and IL-10-independent mechanisms. Infect Immun. 2009;77:5347-58.
181. Imai S, Tezuka H, Fujita K. A factor of inducing IgE from a filarial parasite prevents insulin-dependent diabetes mellitus in nonobese diabetic mice. Biochem Biophys Res Commun. 2001;286:1051-8.
182. Wang B, Geng YB, Wang CR. CD1-restricted NK T cells protect nonobese diabetic mice from developing diabetes. J Exp Med. 2001;194:313-20.
183. Daveson AJ, Jones DM, Gaze S, McSorley H, Clouston A, Pascoe A, et al. Effect of hookworm infection on wheat challenge in celiac disease-a randomised double-blinded placebo controlled trial. PLoS One. 2011;6:e17366.
184. McSorley HJ, Gaze S, Daveson J, Jones D, Anderson RP, Clouston A, et al. Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection. PLoS One. 2011;6:e24092.
185. Miyake K, Adachi K, Watanabe M, Sasatomi Y, Ogahara S, Abe Y, et al. Parasites alter the pathological phenotype of lupus nephritis. Autoimmunity. 2014;47:538-47.
186. Nagayama Y, Watanabe K, Niwa M, McLachlan SM, Rapoport B. Schistosoma mansoni and alpha-galactosylceramide: prophylactic effect of Th1 Immune suppression in a mouse model of Graves' hyperthyroidism. J Immunol. 2004;173:2167-73.
187. Atochina O, Harn D. Prevention of psoriasis-like lesions development in fsn/fsn mice by helminth glycans. Exp Dermatol. 2006;15:461-8.
188. Ben-Ami Shor D, Bashi T, Lachnish J, Fridkin M, Bizzaro G, Barshak I, et al. Phosphorylcoline-tuftsin compound prevents development of dextransulfate-sodium-salt induced murine colitis: implications for the treatment of human inflammatory bowel disease. J Autoimmun. 2015;56:111-7.