Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-24T05:09:06.089Z Has data issue: false hasContentIssue false
  • English
  • Français

The benign helminth Hymenolepis diminuta ameliorates chemically induced colitis in a rat model system

Published online by Cambridge University Press:  18 June 2018

Kateřina Jirků Pomajbíková ,
Milan Jirků ,
Jana Levá ,
Kateřina Sobotková ,
Evan Morien  and
Laura Wegener Parfrey Open the ORCID record for Laura Wegener Parfrey [Opens in a new window]
Kateřina Jirků Pomajbíková*
Affiliation:
Biology Centre, Czech Academy of Sciences, Institute of Parasitology, Branišovská 31, 370 05 České Budějovice, Czech Republic Department of Medical Biology, Faculty of Science, University of South-Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic
Milan Jirků
Affiliation:
Biology Centre, Czech Academy of Sciences, Institute of Parasitology, Branišovská 31, 370 05 České Budějovice, Czech Republic
Jana Levá
Affiliation:
Biology Centre, Czech Academy of Sciences, Institute of Parasitology, Branišovská 31, 370 05 České Budějovice, Czech Republic Department of Medical Biology, Faculty of Science, University of South-Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic
Kateřina Sobotková
Affiliation:
Biology Centre, Czech Academy of Sciences, Institute of Parasitology, Branišovská 31, 370 05 České Budějovice, Czech Republic
Evan Morien
Affiliation:
Department of Botany, Biodiversity Research Centre, University of British Columbia, 3200-6270 University Boulevard BC V6T 1Z4, Vancouver, Canada
Laura Wegener Parfrey*
Affiliation:
Department of Botany, Biodiversity Research Centre, University of British Columbia, 3200-6270 University Boulevard BC V6T 1Z4, Vancouver, Canada Department of Zoology, University of British Columbia, 4200-6270 University Boulevard BC V6T 1Z4, Vancouver, Canada
*
Author for correspondence: Laura Wegener Parfrey, Kateřina Jirků Pomajbíková, E-mail: [email protected], [email protected]
Author for correspondence: Laura Wegener Parfrey, Kateřina Jirků Pomajbíková, E-mail: [email protected], [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

The tapeworm Hymenolepis diminuta is a model for the impact of helminth colonization on the mammalian immune system and a candidate therapeutic agent for immune mediated inflammatory diseases (IMIDs). In mice, H. diminuta protects against models of inflammatory colitis by inducing a strong type 2 immune response that is activated to expel the immature worm. Rats are the definitive host of H. diminuta, and are colonized stably and over long time periods without harming the host. Rats mount a mild type 2 immune response to H. diminuta colonization, but this response does not generally ameliorate colitis. Here we investigate the ability of different life cycle stages of H. diminuta to protect rats against a model of colitis induced through application of the haptenizing agent dinitrobenzene sulphonic acid (DNBS) directly to the colon, and monitor rat clinical health, systemic inflammation measured by TNFα and IL-1β, and the gut microbiota. We show that immature H. diminuta induces a type 2 response as measured by increased IL-4, IL-13 and IL-10 expression, but does not protect against colitis. In contrast, rats colonized with mature H. diminuta and challenged with severe colitis (two applications of DNBS) have lower inflammation and less severe clinical symptoms. This effect is not related the initial type 2 immune response. The gut microbiota is disrupted during colitis and does not appear to play an overt role in H. diminuta-mediated protection.

Keywords

Benign helminthDNBS colitisgut microbiotahelminth therapyHymenolepis diminutaIL-10 cytokinesTNFα
Type
Special Issue Research Article
Information
Parasitology , Volume 145 , Special Issue 10: Parasites and their (endo)symbiotic microbes , September 2018 , pp. 1324 - 1335
Check for updates
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Allen, JE and Maizels, RM (2011) Diversity and dialogue in immunity to helminths. Nature Reviews Immunology 11, 375–388.Google Scholar
Anderson, JL, Edney, RJ and Whelan, K (2012) Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 36, 503–516.Google Scholar
Berger, SA, Krompass, D and Stamatakis, A (2011) Performance, accuracy, and Web server for evolutionary placement of short sequence reads under maximum likelihood. Systematic Biology 60, 291–302.Google Scholar
Blaser, MJ (2014) Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues. New York: Henry Holt & Company.Google Scholar
Bray, JR and Curtis, JT (1957) An ordination of upland forest communities of southern Wisconsin. Ecological Monographs 27, 325–349.Google Scholar
Caporaso, JG, Bittinger, K, Bushman, FD, DeSantis, TZ, Andersen, GL and Knight, R (2010 a) PyNAST: a flexible tool for aligning sequences to a template alignment. Bioinformatics 26, 266–267.Google Scholar
Caporaso, JG, Kuczynski, J, Stombaugh, J, Bittinger, K, Bushman, FD, Costello, EK, Fierer, N, Pena, AG, Goodrich, JK, Gordon, JI, Huttley, GA, Kelley, ST, Knights, D, Koenig, JE, Ley, RE, Lozupone, CA, McDonald, D, Muegge, BD, Pirrung, M, Reeder, J, Sevinsky, JR, Tumbaugh, PJ, Walters, WA, Widmann, J, Yatsunenko, T, Zaneveld, J and Knight, R (2010 b) QIIME allows analysis of high-throughput community sequencing data. Nature Methods 7, 335–336.Google Scholar
Chao, A (1984) Non-parametric estimation of the number of classes in a population. Scandinavian Journal of Statistics 11, 265–270.Google Scholar
Cheng, A, Jaint, D, Thomas, S, Wilson, J and Parker, W (2015) Overcoming evolutionary mismatch by self-treatment with helminths: current practices and experience. Journal of Evolutionary Medicine 3, art235910.Google Scholar
Chudnovskiy, A, Mortha, A, Kana, V, Kennard, A, Ramirez, JD, Rahman, A, Remark, R, Mogno, I, Ng, R, Gnjatic, S, Amir, ED, Solovyov, A, Greenbaum, B, Clemente, J, Faith, J, Belkaid, Y, Grigg, ME and Merad, M (2016) Host-protozoan interactions protect from mucosal infections through activation of the inflammasome. Cell 167, 444–456 e414.Google Scholar
Clemente, JC, Ursell, LK, Parfrey, LW and Knight, R (2012) The impact of the gut microbiota on human health: an integrative view. Cell 148, 1258–1270.Google Scholar
Cooper, P, Walker, AW, Reyes, J, Chico, M, Salter, SJ, Vaca, M and Parkhill, J (2013) Patent human infections with the whipworm, Trichuris trichiura, are not associated with alterations in the faecal microbiota. PLoS ONE 8, e76573.Google Scholar
Edgar, RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26, 2460–2461.Google Scholar
Ehret, T, Torelli, F, Klotz, C, Pedersen, AB and Seeber, F (2017) Translational rodent models for research on parasitic protozoa-A review of confounders and possibilities. Frontiers in cellular and infection microbiology 7, 238.Google Scholar
El-Gabalawy, H, Guenther, LC and Bernstein, CN (2010) Epidemiology of immune-mediated inflammatory diseases: incidence, prevalence, natural history, and comorbidities. Journal of Rheumatology Supplement 85, 2–10.Google Scholar
Elliott, DE and Weinstock, JV (2012) Where are we on worms? Current Opinion in Gastroenterology 28, 551–556.Google Scholar
Eren, AM, Morrison, HG, Lescault, PJ, Reveillaud, J, Vineis, JH and Sogin, ML (2014) Minimum entropy decomposition: unsupervised oligotyping for sensitive partitioning of high-throughput marker gene sequences. The ISME Journal 9, 968.Google Scholar
Fleming, JO and Weinstock, JV (2015) Clinical trials of helminth therapy in autoimmune diseases: rationale and findings. Parasite Immunology 37, 277–292.Google Scholar
Fumagalli, M, Pozzoli, U, Cagliani, R, Comi, GP, Riva, S, Clerici, M, Bresolin, N and Sironi, M (2009) Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. The Journal of Experimental Medicine 206, 1395–1408.Google Scholar
Girgis, NM, Gundra, UM and Loke, P (2013) Immune regulation during helminth infections. PLoS Pathogens 9, e1003250.Google Scholar
Helmby, H (2015) Human helminth therapy to treat inflammatory disorders – where do we stand? BMC Immunology 16, 12.Google Scholar
Hernandez, JL, Leung, G and McKay, DM (2013) Cestode regulation of inflammation and inflammatory diseases. International Journal for Parasitology 43, 233–243.Google Scholar
Hunter, MM, Wang, A, Hirota, CL and McKay, DM (2005) Neutralizing anti-IL-10 antibody blocks the protective effect of tapeworm infection in a murine model of chemically induced colitis. Journal of Immunology 174, 7368–7375.Google Scholar
Iliev, ID and Leonardi, I (2017) Fungal dysbiosis: immunity and interactions at mucosal barriers. Nature Reviews. Immunology 17, 635–646.Google Scholar
Johnston, MJ, Wang, A, Catarino, ME, Ball, L, Phan, VC, MacDonald, JA and McKay, DM (2010) Extracts of the rat tapeworm, Hymenolepis diminuta, suppress macrophage activation in vitro and alleviate chemically induced colitis in mice. Infection and Immunity 78, 1364–1375.Google Scholar
Kostic, AD, Xavier, RJ and Gevers, D (2014) The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 146, 1489–1499.Google Scholar
Lee, SC, Tang, MS, Lim, YA, Choy, SH, Kurtz, ZD, Cox, LM, Gundra, UM, Cho, I, Bonneau, R, Blaser, MJ, Chua, KH and Loke, P (2014) Helminth colonization is associated with increased diversity of the gut microbiota. PLoS Neglected Tropical Diseases 8, e2880.Google Scholar
Lerner, A, Jeremias, P and Matthias, T (2015) The world incidence and prevalence of autoimmune diseases is increasing. International Journal of Celiac Disease 3, 151–155.Google Scholar
Leung, T and Poulin, R (2008) Parasitism, commensalism, and mutualism: exploring the many shades of symbioses. Vie Milieu 58, 107–115.Google Scholar
Liu, J, Morey, RA, Wilson, JK and Parker, W (2017) Practices and outcomes of self-treatment with helminths based on physicians' observations. Journal of Helminthology 91, 267–277.Google Scholar
Lloyd-Price, J, Abu-Ali, G and Huttenhower, C (2016) The healthy human microbiome. Genome Medicine 8, 51.Google Scholar
Lopes, F, Reyes, JL, Wang, A, Leung, G and McKay, DM (2015) Enteric epithelial cells support growth of Hymenolepis diminuta in vitro and trigger Th2-promoting event in a aspecis specific manner. International Journal for Parasitology 45, 691–696.Google Scholar
Love, MI, Huber, W and Anders, S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Bioogyl 15, 550.Google Scholar
Lozupone, C and Knight, R (2005) Unifrac: a new phylogenetic method for comparing microbial communities. Applied and Environmental Microbiology 71, 8228–8235.Google Scholar
Lozupone, CA, Stombaugh, JI, Gordon, JI, Jansson, JK and Knight, R (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230.Google Scholar
Lukeš, J, Kuchta, R, Scholz, T and Pomajbíková, K (2014) (Self-) infections with parasites: re-interpretations for the present. Trends in Parasitology 30, 377–385.Google Scholar
Lukeš, J, Stensvold, CR, Jirků Pomajbíková, K and Parfrey, LW (2015) Are human intestinal eukaryotes beneficial, or commensals? PLoS Pathogens 11, e1005039.Google Scholar
Maizels, RM and McSorley, HJ (2016) Regulation of the host immune system by helminth parasites. Journal of Allergy and Clinical Immunology 183, 666–675.Google Scholar
Mangano, VD and Modiano, D (2014) Host genetics and parasitic infections. Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases 20, 1265–1275.Google Scholar
Martín, R, Chain, F, Miquel, S, Lu, J, Gratadoux, JJ, Sokol, H, Verdu, EF, Bercik, P, Bermudez-Humaran, LG and Langella, P (2014) The commensal bacterium Faecalibacterium prausnitzii is protective in DNBS-induced chronic moderate and severe colitis models. Inflammatory Bowel Diseases 20, 417–430.Google Scholar
McKay, DM (2010) The immune response to and immunomodulation by Hymenolepis diminuta. Parasitology 137, 385–394.Google Scholar
McKay, DM (2015) Not all parasites are protective. Parasite Immunology 37, 324–332.Google Scholar
McKay, DM and Khan, WI (2003) STAT-6 is an absolute requirement for murine rejection of Hymenolepis diminuta. Journal of Parasitology 89, 188–189.Google Scholar
McKenney, EA, Williamson, L, Yoder, AD, Rawls, JF, Bilbo, SD and Parker, W (2015) Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta. Gut Microbes 6, 182–193.Google Scholar
McMurdie, PJ and Holmes, S (2013) Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 8, e61217.Google Scholar
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. Journal of Biomedicine and Biotechnology 2010, article ID 384523, 7. doi: 10.1155/2010/384523.Google Scholar
Molodecky, NA, Soon, I. S., Rabi, D. M., Ghali, W. A., Ferris, M., Chernoff, G., Benchimol, E. I., Panaccione, R., Ghosh, S., Barkema, H. W. and Kaplan, G. G. (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142, 46–54.e42; quiz e30.Google Scholar
Oksanen, J, Blanchet, F. G., Friendly, M., Kindt, R., Legendre, P., McGlinn, D., Minchin, P. R., O'Hara, R. B., Simpson, G. L., Solymos, P., Stevens, M. H. H., Szoecs, E. and Wagner, H.(2017). vegan: Community Ecology Package. R Package version 2.4-3.Google Scholar
Osborne, LC, Monticelli, LA, Nice, TJ, Sutherland, TE, Siracusa, MC, Hepworth, MR, Tomov, VT, Kobuley, D, Tran, SV, Bittinger, K, Bailey, AG, Laughlin, AL, Boucher, JL, Wherry, EJ, Bushman, FD, Allen, JE, Virgin, HW and Artis, D (2014) Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Science 345, 578–582.Google Scholar
Parfrey, L, Jirků, M, Šíma, R, Jalovecká, M, Sak, B, Grigore, K and Jirků Pomajbíková, K (2017) A benign helminth alters the host immune system and the gut microbiota in a rat model system. PLoS ONE 12, e0182205.Google Scholar
Parker, W and Ollerton, J (2013) Evolutionary biology and anthropology suggest biome reconstitution as a necessary approach toward dealing with immune disorders. Evolution, Medicine and Public Health 2013, 89–103.Google Scholar
Persaud, R, Wang, A, Reardon, C and McKay, DM (2007) Characterization of the immuno-regulatory response to the tapeworm Hymenolepis diminuta in the non-permissive mouse host. International Journal for Parasitology 37, 393–403.Google Scholar
Pfaffl, MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research 29, e45.Google Scholar
Ponder, A and Long, MD (2013) A clinical review of recent findings in the epidemiology of inflammatory bowel disease. Clinical Epidemiology 5, 237–247.Google Scholar
Quast, C, Pruesse, E, Yilmaz, P, Gerken, J, Schweer, T, Yarza, P, Peplies, J and Glockner, FO (2013) The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Research 41, D590–D596.Google Scholar
R_Core_Team (2013) R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing.Google Scholar
Ramanan, D, Bowcutt, R, Lee, SC, Tang, MS, Kurtz, ZD, Ding, Y, Honda, K, Gause, WC, Blaser, MJ, Bonneau, RA, Lim, YA, Loke, P and Cadwell, K (2016) Helminth infection promotes colonization resistance via type 2 immunity. Science 352, 608–612.Google Scholar
Reyes, JL, Wang, A, Fernando, MR, Graepel, R, Leung, G, van Rooijen, N, Sigvardsson, M and McKay, DM (2015) Splenic B cells from Hymenolepis diminuta-infected mice ameliorate colitis independent of T cells and via cooperation with macrophages. Journal of Immunology 194, 364–378.Google Scholar
Reyes, JL, Fernando, MR, Lopes, F, Leung, G, Mancini, NL, Matisz, CE, Wang, A and McKay, DM (2016) IL-22 restrains tapeworm-mediated protection against experimental colitis via regulation of IL-25 expression. PLoS Pathogens 12, e1005481.Google Scholar
Reynolds, LA, Smith, KA, Filbey, KJ, Harcus, Y, Hewitson, JP, Redpath, SA, Valdez, Y, Yebra, MJ, Finlay, BB and Maizels, RM(2014) Commensal-pathogen interactions in the intestinal tract: lactobacilli promote infection with, and are promoted by, helminth parasites. Gut Microbes 5, 522–532.Google Scholar
Reynolds, LA, Finlay, BB and Maizels, RM (2015) Cohabitation in the intestine: interactions among helminth parasites, bacterial microbiota, and host immunity. Journal of Immunology 195, 4059–4066.Google Scholar
Roberts, LS (1980) Development of Hymenolepis diminuta in its definitive host. In Arai, H (ed.), Biology of the Tapeworm Hymenolepis Diminuta. New York: Academic Press, pp. 357–423.Google Scholar
Rook, GAW, Raison, CL and Lowry, CA (2014) Microbial ‘old friends’, immunoregulation and socioeconomic status. Clinical & Experimental Immunology 177, 1–12.Google Scholar
Rossen, NG, Bart, A, Verhaar, N, van Nood, E, Kootte, R, de Groot, PF, D'Haens, GR, Ponsioen, CY and van Gool, T (2015) Low prevalence of Blastocystis sp. in active ulcerative colitis patients. European Journal of Clinical Microbiology & Infectious Diseases: Official Publication of the European Society of Clinical Microbiology 34, 1039–1044.Google Scholar
Sartor, RB and Mazmanian, SK (2012) Intestinal microbes in inflammatory bowel diseases. American Journal of Gastroenterology Supplements 1, 15.Google Scholar
Smyth, K, Morton, C, Mathew, A, Karuturi, S, Haley, C, Zhang, M, Holzknecht, ZE, Swanson, C, Lin, SS and Parker, W (2017) Production and use of Hymenolepis diminuta cysticercoids as anti-inflammatory therapeutics. Journal of Clinical Medicine 6, 98.Google Scholar
Team, RC (2016) R: A Language Environment for Statistical Computing. Vienna, Austria: R Foundation for Staticistical Computing.Google Scholar
Velasquez-Manoff, M (2012) An Epidemic of Absence. New York: Scribner.Google Scholar
Wallace, JL, Le, T., Carter, L., Appleyard, C. B. and Beck, P. L. (1995) Hapten-induced chronic colitis in the rat: alternatives to trinitrobenzene sulfonic acid. Journal of Pharmacological and Toxicological Methods 33, 237–239.Google Scholar
Wang, A and McKay, DM (2005) Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta. Parasitology 130, 575–585.Google Scholar
Wang, A, Fernando, M, Leung, G, Phan, V, Smyth, D and McKay, DM (2010) Exacerbation of oxazolone colitis by infection with the helminth Hymenolepis diminuta. American Journal of Pathology 177, 2850–2859.Google Scholar
Wang, M, Wu, L, Weng, R, Zheng, W, Wu, Z and Lv, Z (2017) Therapeutic potential of helminths in autoimmune diseases: helminth-derived immune-regulators and immune balance. Parasitology Research 116, 2065–2074.Google Scholar
Webb, RA, Hoque, T and Dimas, S (2007) Expulsion of the gastrointestinal cestode, Hymenolepis diminuta by tolerant rats: evidence for mediation by a Th2 type immune enhanced goblet cell hyperplasia, increased mucin production and secretion. Parasite Immunology 29, 11–21.Google Scholar
Wickham, H (2009) ggplot2: Elegant Graphics for Data Analysis. New York: Springer-Verlag.Google Scholar
Williamson, LL, McKenney, EA, Holzknecht, ZE, BElliveau, C, Rawls, JF, Poulton, S, Parker, W and Bilbo, SD (2016) Got worms? Perinatal exposure to helminth prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection. Brain, Behaviour and Immunity 51, 14–25.Google Scholar
Zaiss, MM and Harris, NL (2016) Interactions between the intestinal microbiome and helminth parasites. Parasite Immunology 38, 5–11.Google Scholar
Zaiss, MM, Rapin, A, Lebon, L, Dubey, LK, Mosconi, I, Sarter, K, Piersigilli, A, Menin, L, Walker, AW, Rougemont, J, Paerewijck, O, Geldhof, P, McCoy, KD, Macpherson, AJ, Croese, J, Giacomin, PR, Loukas, A, Junt, T, Marsland, BJ and Harris, NL (2015) The intestinal microbiota contributes to the ability of helminths to modulate allergic inflammation. Immunity 43, 998–1010.Google Scholar
Supplementary material: File

Jirků Pomajbíková et al. supplementary material

Jirků Pomajbíková et al. supplementary material 1

Download Jirků Pomajbíková et al. supplementary material(File)
File 3.1 MB