Skip to main content Accessibility help

The immune response to and immunomodulation by Hymenolepis diminuta

  • DEREK M. McKAY (a1)


Analyses of laboratory-based helminth-rodent model systems have been immensely useful in delineating the workings of the mammalian immune system. Investigations in the 1970s–1980s on the fate of the rat tapeworm, Hymenolepis diminuta, in rats and mice and the systemic and local responses evoked following infection have contributed directly to our knowledge of how permissive and non-permissive hosts respond to the challenge of infection with a helminth parasite. This convenient laboratory model system has, in the authors' opinion, regrettably received considerably less attention in recent years. With the goal of highlighting the utility of this model system, data is presented on: (1) the immune and enteric responses of rats and mice to infection with H. diminuta; (2) the ability of excretory or secretory products derived from H. diminuta to significantly reduce T cell and macrophage activation in vitro; and (3) how assessment of H. diminuta-rodent models can be used to identify immune effector or regulatory mechanisms that can be translated into novel treatments for inflammatory and autoimmune disorders.


Corresponding author

Corresponding author: Derek M. McKay, PhD., GIRG, HSC 1717, Univeristy of Calgary, 3330 Hospital Drive NW, Calgary, AlbertaCanada, T2N 4N1. Tel: (403)-220-7362. Fax: (403)-283-3028. Email:


Hide All
Andreassen, J., Bennet-Jenkins, E. M. and Bryant, C. (1999). Immunology and biochemistry of Hymenolepis diminuta. Advances in Parasitology 42, 223275.
Andreassen, J., Hindsbo, O. and Vienberg, S. (1982). Responsiveness of congenitally thymus deficient nude mice to the intestinal cestode, Hymenolepis diminuta. International Journal for Parasitology 12, 215219.
Andreassen, J. and Hopkins, C. A. (1980). Immunologically mediated rejection of Hymenolepis diminuta by its normal host, the rat. Journal of Parasitology 66, 898903.
Bach, J.-F. (2002). The effect of infections on susceptibility to autoimmune and allergic diseases. New England Journal of Medicine 347, 911–20.
Barton-Behravesh, C., Mayberry, L. F., Bristol, J. R., Cardenas, V. M., Mena, K. D., Martíenez-Ocaña, J., Flisser, A. and Snowden, K. F. (2008). Population-based survey of taeniasis along the United States-Mexico border. Annals of Tropical Medicine and Parasitology 102, 325333.
Befus, A. D. and Threadgold, L. T. (1975). Possible immunological damage to the tegument of Hymenolepis diminuta in mice and rats. Parasitology 71, 525534.
Cabello, F. C. (2007) Aquaculture and public health. The emergence of diphyllobothriasis in Chile and the world. Reviews in Medicine (Chile) 135, 10641071.
Christie, P. R., Wakelin, D. and Wilson, M. M. (1979). The effect of the expulsion phase of Trichinella spiralis on Hymenolepis diminuta infection in rats. Parasitology 78, 323330.
Collins, S. M., Blennerhassett, P. A., Blennerhassett, M. G. and Vermillion, D. L. (1989). Impaired acetylcholine release from the myenteric plexus of Trichinella-infected rats. American Journal of Physiology Gastrointestinal and Liver Physiology 257, G898G903.
Dwinell, M. B., Bass, P., Schaefer, D. M. and Oaks, J. A. (1997). Tapeworm infection decreases intestinal transit and enteric aerobic bacterial populations. American Journal of Physiology Gastrointestinal and Liver Physiology 273, G480G485.
Elliott, D. E., Setiawan, T., Metwali, A., Blum, A., Urban, J. F. (Jr.) and Weinstock, J. V. (2004). Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. European Journal of Immunology 34, 26902698.
Elliott, D. E., Summers, R. W. and Weinstock, J. V. (2007). Helminths as governors of immune-mediated inflammation. International Journal for Parasitology 37, 457464.
Fallon, P. G. and Alcami, A. (2006). Pathogen-derived immunomodulatory molecules: future immunotherapeutics? Trends in Immunology 27, 470476.
Fallon, P. G., Ballantyne, S. J., Mangan, N. E., Barlow, J. L., Dasvarma, A., Hewett, D. R., McIlgorm, A., Jolin, H. E. and McKenzie, A. N. (2006). Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. Journal of Experimental Medicine 203, 11051116.
Goodridge, H. S., Stepek, G., Harnett, W. and Harnett, M. M. (2005). Signaling mechanisms underlying subversion of the immune response by the filarial nematode secreted product ES-62. Immunology 115, 296304.
Harnett, W. and Harnett, M. M. (2006). Filarial nematode secreted product ES-62 is an anti-inflammatory agent: therapeutic potential of small molecule derivatives and ES-62 peptide mimetics. Clinical and Experimental Pharmacology and Physiology 33, 511518.
Harnett, W. and Harnett, M. M. (2008) Therapeutic immunomodulators from nematode parasites. Expert Reviews in Molecular Medicine 10, e18e25.
Hopkins, C. A. (1982). Immunological memory in mice to adult Hymenolepis diminuta (Cestoda). Journal of Parasitology 68, 3238.
Hopkins, C. A., Subramanian, G. and Stallard, H. (1972 a). The development of Hymenolepis diminuta in primary and secondary infections in mice. Parasitology 64, 401412.
Hopkins, C. A., Subramanian, G. and Stallard, H. (1972 b). The effect of immunosuppressants on the development of Hymenolepis diminuta in mice. Parasitology 65, 111120.
Hunter, M. M., Wang, A., Hirota, C. L. and McKay, D. M. (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, 73687375.
Hunter, M. M., Wang, A. and McKay, D. M. (2007). Helminth infection enhances disease in a murine TH2 model of colitis. Gastroenterology 132, 13201330.
Isaak, D. D. (1983). In vitro tapeworm extract-induced proliferative responses of gut-associated lymphoid cells from Hymenolepis diminuta infected mice. Journal of Helminthology 57, 4350.
Isaak, D. D., Jacobson, R. H. and Reed, N. D. (1975). Thymus dependence of tapeworm (Hymenolepis diminuta) elimination from mice. Infection and Immunity 12, 14781479.
Johnston, M. J. G., MacDonald, J. A. and McKay, D. M. (2009). Parasitic helminths: a pharmacopeia of anti-inflammatory molecules. Parasitology 136, 125147.
Lundgren, O. (1998). 5-hydroxytryptamine, enterotoxins, and intestinal fluid secretion. Gastroenterology 115, 10091012.
Maizels, R. M. (2005). Infections and allergy – helminths, hygiene and host immune regulation. Current Opinion in Immunology 17, 656661.
McCaigue, M. D. and Halton, D. W. (1987). Immunological damage to Hymenolepis diminuta following a challenge infection in C57 mice. International Journal for Parasitology 17, 795803.
McKay, D. M. (2009) The therapeutic helminth? Trends in Parasitology 25, 109114.
McKay, D. M. and Fairweather, I. (1997). A role for the enteric nervous system in the response to helminth infections. Parasitology Today 13, 6369.
McKay, D. M., Halton, D. W., Johnston, C. F., Fairweather, I. and Shaw, C. (1990 a) Hymenolepis diminuta: changes in intestinal morphology and the enterochromaffin cell population associated with infection in male C57 mice. Parasitology 101, 107113.
McKay, D. M., Halton, D. W., McCaigue, M. D., Johnston, C. F., Fairweather, I. and Shaw, C. (1990 b) Hymenolepis diminuta: Intestinal goblet cell response in male C57 mice. Experimental Parasitology 71, 9–20.
McKay, D. M., Halton, D. W., Shaw, C., Johnston, C. F., Fairweather, I. and Buchanan, K. D. (1991) Hymenolepis diminuta: changes in the levels of certain intestinal regulatory peptides in infected C57 mice. Experimental Parasitology 73, 5–26.
McKay, D. M. and Khan, W. I. (2003). STAT-6 is an absolute requirement for murine rejection of Hymenolepis diminuta. Journal of Parasitology 89, 188189.
McKay, D. M. and Wallace, J. L. (2009). Acetic acid induced gastric ulceration in rats is not affected by infection with Hymenolepis diminuta. Journal of Parasitology 95, 481482.
Moro, P. and Schantz, P. M. (2009). Echinococcosis: a review. International Journal of Infectious Diseases 13, 125133.
Motomura, Y., Ghia, J. E., Wang, H., Akiho, H., El-Sharkawy, R. T., Collins, S. M., Wan, Y., McLaughlin, J. T. and Khan, W. I. (2008). Enterochromaffin cell and 5-hydroxytryptamine responses to the same infectious agent differ in Th1 and Th2 dominant environments. Gut 57, 475481.
Motomura, Y., Wang, H., Deng, Y., El-Sharkawy, R. T., Verdu, E. F. and Khan, W. I. (2009) Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis. Clinical and Experimental Immunology 155, 8895.
Palmas, C., Bortoletti, G., Gabriele, F., Wakelin, D. and Conchedda, M. (1997). Cytokine production during infection with Hymenolepis diminuta in Balb/c mice. International Journal for Parasitology 27, 855859.
Persaud, R., Wang, A., Reardon, C. and McKay, D. M. (2007) Characterization of the immuno-regulatory response to the tapeworm Hymenolepis diminuta in the non-permissive mouse host. International Journal for Parasitology 37, 393403.
Reardon, C., Sanchez, A., Hogaboam, C. M. and McKay, D. M. (2001). Tapeworm infection reduces the ion transport abnormalities induced by dextran sulphate sodium (DSS) colitis. Infection and Immunity 69, 44174423.
Reyes, J. L. and Terrazas, L. I. (2007). The divergent roles of alternatively activated macrophages in helminthic infections. Parasite Immunology 29, 609619.
Setiawan, T., Metwali, A., Blum, A. M., Ince, M. N., Urban, J. F. (Jr.), Elliott, D. E. and Weinstock, J. V. (2007) Heligmosomoides polygyrus promotes regulatory T-cell cytokine production in the murine normal distal intestine. Infection and Immunity 75, 46554663.
Silver, B. B., Dick, T. A. and Welch, H. E. (1980). Concurrent infections of Hymenolepis diminuta and Trichinella spiralis in the rat intestine. Journal of Parasitology 66, 786791.
Smith, P., Mangan, N. E. and Fallon, P. G. (2009). Generation of parasite antigens for use in Toll-like receptor research. Methods in Molecular Biology 517, 401413.
Smyth, J. D. (1994). Cestoda: Cyclophyllidea. In An Introduction to Parasitology, 3rd edition, pp. 321326. Cambridge University Press, Cambridge.
Starke, W. A. and Oaks, J. A. (2001). Ileal mucosal mast cell, eosinophil, and goblet cell populations during Hymenolepis diminuta infection of the rat. Journal of Parasitology 87, 12221225.
Starke-Buzetti, W. A. and Oaks, J. A. (2008). Increased glial-derived neurotrophic factor in the small intestine of rats infected with the tapeworm, Hymenolepis diminuta. International Journal of Pathology 89, 458465.
Summers, R. W., Elliott, D. E., Urban, J. F.(Jr.), Thompson, R. and Weinstock, J. V. (2005). Trichuris suis therapy in Crohn's disease. Gut 54, 8790.
van der Kleij, D., Latz, E., Brouwers, J. F. H. M., Kruize, Y. C. M., Schmitz, M., Kurt-Jones, E. A., Espevik, T., De Jong, E. C., Kapsenberg, M. L., Golenbock, D. T., Tielens, A. G. M. and Yazdanbakhsh, M. (2002). A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization. Journal of Biological Chemistry 277, 4812248129.
Wang, A. and McKay, D. M. (2005). Immune modulation by a high molecular weight protein from the rat tapeworm Hymenolepis diminuta. Parasitology 130, 575585.
Webb, R. A., 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, 1121.
Wilson, M. S. and Maizels, R. M. (2006). Regulatory T cells induced by parasites and the modulation of allergic responses. Chemical Immunology and Allergy 90, 176195.
Wood, J. D. (1993). Neuro-immunophysiology of colon function. Pharmacology 47, 7–13.
Zimmerman, N. P., Brownfield, M. S., DeVente, J., Bass, P. and Oaks, J. A. (2008). cGMP secreted from the tapeworm Hymenolepis diminuta is a signal molecule to the host intestine. Journal of Parasitology 94, 771779.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed