Helminth therapy: Advances in the use of parasitic worms against Inflammatory Bowel Diseases and its challenges

Helminthologia - Tập 55 Số 1 - Trang 1-11 - 2018
Marta Maruszewska‐Cheruiyot1, Katarzyna Donskow‐Łysoniewska1, Maria Doligalska1
1Department of Parasitology, Faculty of Biology University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland

Tóm tắt

Summary

Development of modern medicine and better living conditions in the 20th century helped in reducing a number of cases of infectious diseases. During the same time, expansion of autoimmunological disorders was noticed. Among other are Inflammatory Bowel Diseases (IBD) including ulcerative colitis and Crohn’s disease which are chronic and relapsing inflammation of the gastrointestinal tract. Absence of effective treatment in standard therapies effects the search for alternative opportunities. As per hygienic hypothesis increasing number of cases of autoimmune diseases is as a result of reduced exposure to pathogens, especially parasites. Thus, one of the promising remedial acts against IBD and other allergic and autoimmune disorders is “helminth therapy”. Cure with helminths seems to be the most effective therapy of IBD currently proposed. Helminth therapy focuses on advantageous results that have been obtained from the clinical trials, but its mechanisms are still unclear. Explanation of this phenomenon would help to develop new drugs against IBD based on helminth immunomodulatory molecules.

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Tài liệu tham khảo

Adisakwattana, P., Nuamtanong, S., Kusolsuk, T., Chairoj, M., Yenchitsomanas, P.T., Chaisri, U. (2013): Non-encapsulated Trichinella spp., T. papuae, diminishes severity of DSS-induced colitis in mice. Asian Pac. J. Allergy Immunol., 31: 106 – 114. DOI: 10.12932/AP0238.31.2.201310.12932/AP0238.31.2.2013

Allen, J.E., Maizels, R.M. (2011): Diversity and dialogue in immunity to helminths. Nat. Rev. Immunol., 11: 375 – 388. DOI: 10.1038/nri299210.1038/nri2992

Barthlott, T., Kassiotis, G., Stockinger, B. (2003): T cell regulation as a side effect of homeostasis and competition. J. Exp. Med., 197: 451 – 460. doi: 10.1084/jem.2002138710.1084/jem.20021387

Bernstein, R.M. (2001): Injections and surgical therapy in chronic pain. Clin. J. Pain., 17: 94 – 10410.1097/00002508-200112001-00018

Biedermann, L., Zeitz, J., Mwinyi, J., Sutter-Minder, E., Rehman, A., Ott, S. J., Steurer-Stey, C., Frei, A., Frei, P., Scharl, M., Loessner, M. J., Vavricka, S. R., Fried, M., Schreiber, S., Schuppler, M., Rogler, G. (2013) : Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans. PLoS One, 8: e59260. DOI: 10.1371/journal.pone.0059260

Bilbo, S.D., Wray, G.A., Perkins, S.E., Parker, W. (2011): Reconstitution of the human biome as the most reasonable solution for epidemics of allergic and autoimmune diseases. Med. Hypotheses., 77: 494 – 504. DOI: 10.1016/j.mehy.2011.06.01910.1016/j.mehy.2011.06.019

Blum, A.M., Hang, L., Setiawan, T.,. Urban, J.P., Stoyanoff, K.M., Leung, J., Weinstock, J.V. (2012): Heligmosomoides polygyrus bakeri induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut T cell responses. J. Immunol., 189 (5): 2512 – 2520. DOI: 10.4049/jimmunol.110289210.4049/jimmunol.1102892

Bodammer, P., Waitz, G., Loebermann, M., Holtfreter, M.C., Maletzki, C., Krueger, M.R., Nizze, H., Emmrich, J., Reisinger, E.C. (2011): Schistosoma mansoni infection but not egg antigen promotes recovery from colitis in outbred NMRI mice. Dig. Dis. Sci., 56: 70 – 78. DOI: 10.1007/s10620-010-1237-y10.1007/s10620-010-1237-y

Brandtzaeg, P., Haraldsen, G., Rugtveit, J. (1997): Immunopathology of human inflammatory bowel disease. Springer Semin. Immunopathol., 18: 555 – 589. DOI: 10.1007/BF0082405810.1007/BF00824058

Broadhurst, M.J., Ardeshir, A., Kanwar, B., Mirpuri, J., Gundra, U.M., Leung, J.M., Wiens, K.E., Vujkovic-Cvijin, I., Kim, C.C., Yarovinsky, F., Lerche, N.W., McCune, J.M., Loke, P. (2012): Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon. PLoS Pathog., 8: e1003000. DOI: 10.1371/journal.ppat.1003000

Cader, M.Z., Kaser, A. (2013): Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation. Gut, 62: 1653 – 1664. DOI: 10.1136/gutjnl-2012-30395510.1136/gutjnl-2012-303955

Chandrashekara, S. (2012): The treatment strategies of autoimmune disease may need a different approach from conventional protocol: A review. Indian J. Pharmacol., 44: 665 – 671. DOI: 10.4103/0253-7613.10323510.4103/0253-7613.103235

Chassaing, B., Aitken, J.D., Malleshappa, M., Vijay-Kumar, M. (2015): Dextran sulfate sodium (DSS)-induced colitis in mice. Curr. Protoc. Immunol., 104: 15 – 25. DOI: 10.1002/0471142735.im1525s10410.1002/0471142735.im1525s104

Chen, C.C., Louie, S., McCormick, B., Walker, W.A., Shi, H.N. (2005): Concurrent infection with an intestinal helminth parasite impairs host resistance to enteric Citrobacter rodentium and enhances Citrobacter-induced colitis in mice. Infect. Immun., 73: 5468 – 5481. DOI: 10.1128/IAI.73.9.5468-5481.200510.1128/IAI.73.9.5468-5481.2005

Chen, C.C., Louie, S., McCormick, B.A., Walker, W.A., Shi, H.N. (2006): Helminth primed dendritic cells alter the host response to enteric bacterial infection. J. Immunol.,176: 472 – 483

Cleynen, I., Boucher, G., Jostins, L. et al. (2016): Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. Lancet, 9, 156 – 167. DOI: 10.1016/S0140-6736(15)00465-110.1016/S0140-6736(15)00465-1

Correale, J. (2014): Helminth/Parasite treatment of multiple sclerosis. Curr. Treat Options Neurol.,16: 296. DOI: 10.1007/s11940-014-0296-310.1007/s11940-014-0296-3

Croese, J., Giacomin, P., Navarro, S., Clouston, A., McCann, L., Dougall, A., Ferreira, I., Susianto, A., O’Rourke, P., Howlett, M., McCarthy, J., Engwerda, C., Jones, D., Loukas, A. (2015): Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J. Allergy Clin. Immunol.,135: 508 – 516. DOI: 10.1016/j.jaci.2014.07.02210.1016/j.jaci.2014.07.022

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. doi: 10.1136/gut.2005.07912910.1136/gut.2005.079129

Daveson, A.J., Jones, D.M., Gaze, S., McSorley, H., Clouston, A., Pascoe, A., Cooke, S., Speare, R., Macdonald, G.A., Anderson, R., McCarthy, J.S., Loukas, A., Croese, J. (2011): Effect of hookworm infection on wheat challenge in celiac disease – a randomised double-blinded placebo controlled trial. PLoS One, 8: e17366. DOI: 10.1371/journal.pone.0017366

Donskow, K., Drela, N., Doligalska, M. (2011): Heligmosomoides bakeri antigen rescues CD4-positive T cells from glucocorticoid-induced apoptosis by Bcl-2 protein expression. Parasite Immunol., 33: 158 – 169. DOI: 10.1111/j.1365-3024.2010.01262.x10.1111/j.1365-3024.2010.01262.x

Donskow-Łysoniewska, K., Bien, J., Brodaczewska, K., Krawczak, K., Doligalska, M. (2013b): Colitis promotes adaptation of an intestinal nematode: a Heligmosomoides polygyrus mouse model system. PLoS One, 22: e78034. DOI: 10.1371/journal.pone.0078034

Donskow-Łysoniewska, K., Brodaczewska, K., Doligalska, M. (2013a): Heligmosomoides polygyrus antigens inhibit the intrinsic pathway of apoptosis by overexpression of survivin and Bcl-2 protein in CD4 T cells. Prion, 7: 319 – 327. DOI:10.4161/pri.2500810.4161/pri.25008

Donskow-Lysoniewska, K., Majewski, P., Brodaczewska, K., Jozwicka, K., Doligalska, M. (2012): Heligmosmoides polygyrus fourth stages induce protection against DSS induced colitis and change opioid expression in the intestine. Parasite Immunol., 34: 536 – 546. DOI: 10.1111/pim.1200310.1111/pim.12003

Du, L., Tang, H., Ma, Z., Xu, J., Gao, W., Chen, J., Gan, W., Zhang, Z., Yu, X., Zhou, X., Hu, X. (2011): The protective effect of the recombinant 53-kDa protein of Trichinella spiralis on experimental colitis in mice. Dig. Dis. Sci., 56: 2810 – 2817. DOI: 10.1007/s10620-011-1689-810.1007/s10620-011-1689-8

Elliott, D.E., Li, J., Blum, A., Metwali, A., Qadir, K., Urban, J.F. Jr, Weinstock, J.V. (2003): Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am. J. Physiol. Gastrointest. Liver Physiol., 284: G385 – G391. DOI: 10.1152/ajpgi.00049.200210.1152/ajpgi.00049.2002

Elliott, D.E., Metwali, A., Leung, J., Setiawan, T., Blum, A.M., Ince, M.N., Bazzone, L.E., Stadecker, M.J., Urban, J.F. Jr, Weinstock, J.V. (2008): Colonization with Heligmosomoides polygyrus suppresses mucosal IL-17 production. J. Immunol., 181: 2414 – 2419

Elliott, D.E., Setiawan, T., Metwali, A., Blum, A., Urban, J.F. Jr., Weinstock, J.V. (2004): Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Eur. J. Immunol., 34: 2690 – 2698. DOI: 10.1002/eji.200324833

Elliott, D.E., Urban, J.F. Jr., Argo, C.K., Weinstock, J.V. (2000): Does the failure to acquire helminthic parasites predispose to Crohn’s disease? FASEB J., 14: 1848 – 1855. doi: 10.1096/fj.99-0885hyp10.1096/fj.99-0885hyp

Erb, K.J. (2009): Can helminths or helminth-derived products be used in humans to prevent or treat allergic diseases? Trends Immunol., 30: 75 – 82. DOI: 10.1016/j.it.2008.11.00510.1016/j.it.2008.11.005

Finlay, C.M., Walsh, K.P., Mills, K.H. (2014): Induction of regulatory cells by helminth parasites: exploitation for the treatment of inflammatory diseases. Immunol. Rev., 259: 206 – 230. DOI: 10.1111/imr.1216410.1111/imr.12164

Fleming, J.O., Isaak, A., Lee, J.E., Luzzio, C.C., Carrithers, M.D., Cook, T.D., Field, A.S., Boland, J., Fabry, Z. (2011): Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study. Mult. Scler., 17: 743 – 754. DOI: 10.1177/135245851139805410.1177/1352458511398054

Goodridge, H.S., Stepek, G., Harnett, W., Harnett, M.M. (2005): Signalling mechanisms underlying subversion of the immune response by the filarial nematode secreted product ES-62. Immunology, 115: 296 – 304. DOI: 10.1111/j.1365-2567.2005.02167.x10.1111/j.1365-2567.2005.02167.x

Gouy De Bellocq, J., Ferte, H., Depaquit, J., Justine, J.L., Tillier, A., Durette-Desset, M.C. (2001): Phylogeny of the Trichostrongylina (Nematoda) inferred from 28S rDNA sequences. Mol. Phylogenet. Evol., 19: 430 – 442. DOI: 10.1006/mpev.2001.092510.1006/mpev.2001.0925

Hadis, U., Wahl, B., Schulz, O., Hardtke-Wolenski, M., Schippers, A., Wagner, N., Müller, W., Sparwasser, T., Förster, R., Pabst, O. (2011): Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity, 34: 237 – 246. DOI: 10.1016/j.immuni.2011.01.01610.1016/j.immuni.2011.01.016

Hang, L., Setiawan, T., Blum, A.M., Urban, J., Stoyanoff, K., Arihiro, S., Reinecker, H.C., Weinstock, J.V. (2010): Heligmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity. J. Immunol, 185: 3184 – 3189. DOI: 10.4049/jimmunol.100094110.4049/jimmunol.1000941

Helmby, H. (2015): Human helminth therapy to treat inflammatory disorders - where do we stand? BMC Immunol., 16: 12. DOI: 10.1186/s12865-015-0074-310.1186/s12865-015-0074-3

Herrera, L.A., Ostrosky-Wegman, P. (2001): Do helminths play a role in carcinogenesis? Trends Parasitol., 17: 172 – 175. DOI: 10.1016/S1471-4922(00)01942-510.1016/S1471-4922(00)01942-5

Hokke, C.H., Deelder, A.M., Hoffmann, K.F., Wuhrer, M. (2007): Glycomics-driven discoveries in schistosome research. Exp. Parasitol., 117: 275 – 283. DOI: 10.1016/j.exppara.2007.06.00310.1016/j.exppara.2007.06.003

Huby, F., Hoste, H., Mallet, S., Fournel, S., Nano, J.L. (1995): Effects of the excretory/secretory products of six nematode species, parasites of the digestive tract, on the proliferation of HT29-D4 and HGT-1 cell lines. Epithelial Cell Biol., 4: 156 – 162

Hunter, M.M., Wang, A., Hirota, C.L., Mckay, D.M. (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 – 7375. DOI: 10.4049/jimmunol.174.11.7368

Hunter, M.M., Wang, A., Mckay, D.M. (2007): Helminth infection enhances disease in a murine TH2 model of colitis. Gastroenterology, 132: 1320 – 1330. DOI: 10.1053/j.gastro.2007.01.03810.1053/j.gastro.2007.01.038

Ince, M.N., Elliott, D.E., Setiawan, T., Metwali, A., Blum, A., Chen, H.L., Urban, J.F., Flavell, R.A., Weinstock, J.V. (2009): Role of T cell TGF-beta signaling in intestinal cytokine responses and helminthic immune modulation. J. Immunol., 39: 1870 – 1878. DOI: 10.1002/eji.20083895610.1002/eji.200838956

Kappus, K.D., Lundgren, R.G. Jr., Juranek, D.D., Roberts, J.M., Spencer, H.C. (1994): Intestinal parasitism in the United States: update on a continuing problem. Am. J. Trop. Med. Hyg., 50, 705 – 713. DOI: 10.4269/ajtmh.1994.50.70510.4269/ajtmh.1994.50.705

Keubler, L.M., Buettner, M., Häger, C., Bleich, A. (2015): A multihit model: colitis lessons from the Interleukin-10-deficient mouse. Inflamm. Bowel Dis., 2: 1967 – 1975. DOI: 10.1097/MIB.0000000000000468

Khan, A.R., Fallon, P.G. (2013): Helminth therapies: translating the unknown unknowns to known knowns. Int. J. Parasitol., 43: 293 – 299. DOI: 10.1016/j.ijpara.2012.12.00210.1016/j.ijpara.2012.12.002

Khan, W.I., Blennerhasset, P.A., Varghese, A.K., Chowdhury, S.K., Omsted, P., Deng, Y., Collins, S.M. (2002): Intestinal nematode infection ameliorates experimental colitis in mice. Infect. Immun., 70: 5931 – 5937. doi: 10.1128/IAI.70.11.5931-5937.200210.1128/IAI.70.11.5931-5937.2002

Lakatos, P.L. (2006): Recent trends in the epidemiology of inflammatory bowel diseases: up or down? World J. Gastroenterol., 14: 6102-6108. doi: 10.3748/wjg.v12.i38.610210.3748/wjg.v12.i38.6102

Leitner, G.C., Vogelsang, H. (2016): Pharmacological-and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. World J. Gastrointest. Pharmacol. Ther., 6: 5 – 20. DOI: 10.4292/wjgpt.v7.i1.510.4292/wjgpt.v7.i1.5

Leong, R.W., Mitrev, N., Ko, Y. (2016): Hygiene hypothesis: Is the evidence the same all over the world? Dig. Dis., 34: 35 – 42. DOI: 10.1159/00044292210.1159/000442922

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 – 1455. DOI: 10.1002/ibd.2285810.1002/ibd.22858

Li, X., Sundquist, J., Hemminki, K., Sundquist, K. (2011): Risk of inflammatory bowel disease in firstand second-generation immigrants in Sweden: a nationwide follow-up study. Inflamm. Bowel Dis., 17: 1784 – 1791. DOI: 10.1002/ibd.2153510.1002/ibd.21535

MacDonald, T.T., Monteleone, G. (2005): Immunity, inflammation, and allergy in the gut. Science, 25: 1920 – 1925. DOI: 10.1126/science.110644210.1126/.1106442

Maizels, R.M., Balic, A., Gomez-Escobar, N., Nair, M., Taylor, M.D., Allen, J.E. (2004): Helminth parasites – masters of regulation. Immunol. Rev., 201, 89 – 116. DOI: 10.1111/j.0105-2896.2004.00191.x10.1111/j.0105-2896.2004.00191.x

Maizels, R.M., Hewitson, J.P., Smith, K.A. (2012): Susceptibility and immunity to helminth parasites. Curr. Opin. Immunol., 24: 459 – 466. DOI: 10.1016/j.coi.2012.06.00310.1016/j.coi.2012.06.003

Mann, E.R., Li, X. (2014): Intestinal antigen-presenting cells in mucosal immune homeostasis: crosstalk between dendritic cells, macrophages and B-cells. World J. Gastroenterol., 7: 9653 – 9664. DOI: 10.3748/wjg.v20.i29.965310.3748/wjg.v20.i29.9653

McGuckin, M.A., Eri, R., Simms, L.A., Florin, T.H., Radford-Smith, G. (2009): Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm. Bowel Dis., 15: 100 – 113. DOI: 10.1002/ibd.2053910.1002/ibd.20539

McSorley, H.J., Hewitson, J.P., Maizels, R.M. (2013): Immunomodulation by helminth parasites: defining mechanisms and mediators. Int. J. Parasitol., 43: 301 – 310. DOI: 10.1016/j.ijpara.2012.11.01110.1016/j.ijpara.2012.11.011

Melon, A., Wang, A., Phan, V., Mckay, D.M. (2010): Infection with Hymenolepis diminuta is more effective than daily corticosteroids in blocking chemically induced colitis in mice. J. Biomed. Biotechnol., 384523. DOI: 10.1155/2010/38452310.1155/2010/384523

Metwali, A., Setiawan, T., Blum, A.M., Urban, J., Elliott, D.E., Hang, L., Weinstock, J.V. (2006): Induction of CD8+ regulatory T cells in the intestine by Heligmosomoides polygyrus infection. Am. J. Physiol. Gastrointest. Liver Physiol., 291: G253 – G259. DOI: 10.1152/ajpgi.00409.2005

Molodecky, N.A., Soon, I.S., Rabi, D.M., Ghali, W.A., Ferris, M., Chernoff, G., Benchimol, E.I., Panaccione, R., Ghosh, S., Barkema, H.W., Kaplan, G.G. (2012): Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology, 142: 46 – 54. DOI: 10.1053/j.gastro.2011.10.00110.1053/j.gastro.2011.10.001

Monroy, F.G., Enriquez, F.J. (1992): Heligmosomoides polygyrus: a model for chronic gastrointestinal helminthiasis. Parasitol. Today, 8: 49 – 54. DOI: 10.1016/0169-4758(92)90084-F10.1016/0169-4758(92)90084-

Morampudi, V., Bhinder, G., Wu, X., Dai, C., Sham, H.P., Vallance, B.A., Jacobson, K. (2014): DNBS/TNBS colitis models: providing insights into inflammatory bowel disease and effects of dietary fat. J. Vis. Exp., 84: 51297. DOI:10.3791/51297

Moreels, T.G., Nieuwendijk, R.J., De Man, J.G., De Winter, B.Y., Herman, A.G., Van Marck, E.A., Pelckmans, P.A. (2004): 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, 53: 99 – 107

Mulvenna, J., Hamilton, B., Nagaraj, S.H., Smyth, D., Loukas, A., Gorman, J.J. (2009): Proteomics analysis of the excretory/secretory component of the blood-feeding stage of the hookworm, Ancylostoma caninum. Mol. Cell. Proteomics, 8: 109 – 121. DOI: 10.1074/mcp.M800206-MCP200

Niewiadomski, O., Studd, C., Wilson, J., Williams, J., Hair, C., Knight, R., Prewett, E., Dabkowski, P., Alexander, S., Allen, B., Dowling, D., Connell, W., Desmond, P., Bell, S. (2016): Influence of food and lifestyle on the risk of developing inflammatory bowel disease. Intern. Med. J., 46: 669 – 676. DOI: 10.1111/imj.1309410.1111/imj.13094

Packham, G., Stevenson, F.K. (2005): Bodyguards and assassins: Bcl-2 family proteins and apoptosis control in chronic lymphocytic leukaemia. Immunology, 114: 441 – 449. DOI: 10.1111/j.1365-2567.2005.02117.x10.1111/j.1365-2567.2005.02117.x

Prasanphanich, N.S., Mickum, M.L., Heimburg-Molinaro, J., Cummings, R.D. (2013): Glycoconjugates in host-helminth interactions. Front. Immunol., 4: 240. DOI: 10.3389/fimmu.2013.0024010.3389/fimmu.2013.00240

Probert, C.S., Jayanthi, V., Pinder, D., Wicks, A.C., Mayberry, J.F. (1992): Epidemiological study of ulcerative proctocolitis in Indian migrants and the indigenous population of Leicestershire. Gut, 33: 687 – 69310.1136/gut.33.5.687

Reardon, C., Sanchez, A., Hogaboam, C.M., Mckay, D.M. (2001): Tapeworm infection reduces epithelial ion transport abnormalities in murine dextran sulfate sodium induced colitis. Infect. Immun., 69: 4417 – 4423. doi: 10.1128/IAI.69.7.4417-4423.200110.1128/IAI.69.7.4417-4423.2001

Rescigno, M., Di Sabatino, A. (2009): Dendritic cells in intestinal homeostasis and disease. J. Clin. Invest.,119: 2441 – 2450. DOI: 10.1172/JCI3913410.1172/JCI39134

Ruyssers, N.E., De Winter, B.Y., De Man, J.G., Loukas, A., Herman, A.G., Pelckmans, P.A., Moreels, T.G. (2008): Worms and the treatment of inflammatory bowel disease: are molecules the answer? Clin. Dev. Immunol., 567314. DOI: 10.1155/2008/567314

Samuelsson, S. (1976): Ulceros Colit och Proktit [Colitis Ulcerosa and Inflammantion]. University of Uppsala, Uppsala, Sweden (In Swedish)

Sandborn, W.J., Elliott, D.E., Weinstock, J., Summers, R.W., Landry-Wheeler, A., Silver, N., Harnett, M.D., Hanauer, S.B. (2013): Randomised clinical trial: the safety and tolerability of Trichuris suis ova in patients with Crohn’s disease. Aliment. Pharmacol. Ther., 38: 255 – 263. DOI: 10.1111/apt.1236610.1111/apt.12366

Satsangi, J., Silverberg, M.S., Vermeire, S., Colombel, J.F. (2006): The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut, 55: 749 – 753. DOI: 10.1136/gut.2005.08290910.1136/gut.2005.082909

Schnoeller, C., Rausch, S., Pillai, S., Avagyan, A., Wittig, B. M., Loddenkemper, C., Hamann, A., Hamelmann, E., Lucius, R., Hartmann, S. (2008): A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages. J. Immunol., 15: 4265 – 4272. DOI: 10.4049/jimmunol.180.6.4265

Setiawan, T., Metwali, A., Blum, A.M. Nedim Ince, M., Urban Jr., J.F., Elliott, D.E., Weinstock, J.V. (2007): Heligmosomoides polygyrus promotes regulatory T-cell cytokine production in the murine normal distal intestine. Infect. Immun., 75: 4655 – 4663. DOI: 10.1128/IAI.00358-0710.1128/IAI.00358-07

Shorter, R.G., Huizenga, K.A., Spencer, R.J. (1972): A working hypothesis for the etiology and pathogenesis of nonspecific inflammatory bowel disease. Am. J. Dig. Dis., 17: 1024 – 103210.1007/BF02239143

Smith, P., Mangan, N.E., Fallon, P.G. (2009): Generation of parasite antigens for use in Toll-like receptor research. Methods Mol., 517: 401 – 413. DOI: 10.1007/978-1-59745-541-1_2410.1007/978-1-59745-541-1_24

Smith, P., Mangan, N.E., Walsh, C.M., Fallon, R.E., Mckenzie, A.N.J., Van Rooijen, N., Fallon, P.G. (2007): Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J. Immunol., 178: 4557 – 4566. DOI: 10.4049/jimmunol.178.7.455710.4049/jimmunol.178.7.4557

Strachan, D.P. (1989): Hay fever, hygiene and household size. BMJ, 299: 1259 – 1260

Summers, R.W., Elliott, D.E., Qadir, K., Urban, J.F., Thompson, R., Weinstock, J.V. (2003): Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am. J. Gastroenterol., 98, 2034 – 2041. DOI: 10.1111/j.1572-0241.2003.07660.x10.1111/j.1572-0241.2003.07660.x

Summers, R.W., Elliott, D.E., Urban, J.F. Jr., Thompson, R., Weinstock, J.V. (2005a): Trichuris suis therapy in Crohn’s disease. Gut, 54: 87 – 90. DOI: 10.1136/gut.2004.04174910.1136/gut.2004.041749

Summers, R.W., Elliott, D.E., Urban, J.F. Jr., Thompson, R.A., Weinstock, J.V. (2005b): Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology, 128: 825 – 832. DOI: 10.1053/j.gastro.2005.01.00510.1053/j.gastro.2005.01.005

Sutton, T.L., Zhao, A., Madden, K.B., Elfrey, J.E., Tuft, B.A., Sullivan, C.A., Urban, Jr., J.F., Shea-Donohue, T. (2008): Antiinflammatory mechanisms of enteric Heligmosomoides polygyrus infection against trinitrobenzene sulfonic acid-induced colitis in a murine model. Infect. Immun., 76: 4772 – 4782. DOI: 10.1128/IAI.00744-0710.1128/IAI.00744-07

Taylor, M.D., Van Der Werf, N., Maizels, R.M. (2012): T cells in helminth infection: the regulators and the regulated. Trends Immunol., 33: 181 – 189. DOI: 10.1016/j.it.2012.01.00110.1016/j.it.2012.01.001

Wilson, M.S., Maizels, R.M. (2004): Regulation of allergy and autoimmunity in helminth infection. Clin. Rev. Allergy Immunol., 26: 35 – 50. DOI: 10.1385/CRIAI:26:1:3510.1385/CRIAI:26:1:35

Wirtz, S., Neurath, M.F. (2007): Mouse models of inflammatory bowel disease. Adv. Drug Deliv. Rev., 59: 1073 – 1083. DOI: 10.1016/j.addr.2007.07.00310.1016/j.addr.2007.07.003

Xia, C.M., Zhao, Y., Jiang, L., Jiang, J., Zhang, S.C. (2011): Schistosoma japonicum ova maintains epithelial barrier function during experimental colitis. World J Gastroenterol., 17: 4810 – 4816.10.3748/wjg.v17.i43.4810

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 – 1780. DOI: 10.1111/j.1440-1746.2009.05986.x10.1111/j.1440-1746.2009.05986.x