Parasite Challenge as Host Resistance Models for Immunotoxicity Testing

  • Robert W. LuebkeEmail author
Part of the Methods in Molecular Biology™ book series (MIMB, volume 598)


Identification of potentially immunosuppressive compounds typically involves assessing a combination of observational endpoints as surrogates for functional endpoints and functional endpoints as surrogates for resistance to infectious or neoplastic disease. Host resistance assays are considered to be the “gold standard” against which suppression of immune function at the molecular or cellular level can be judged, because resistance to infection, regardless of the actual pathogen, involves multiple pathways of effector function to neutralize or eliminate pathogens. Resistance to infection with the parasitic nematode Trichinella spiralis has been used to assess immune function following exposure to a variety of immunotoxicants at the whole animal level. The various immunological mechanisms that are responsible for resistance to different phases of the life cycle are well documented, as are the effects of immunosuppression on the outcome of infection. This chapter describes methods to assess elimination of adult parasites from the small intestine, body burdens of larvae, as well as antibody responses and lymphocyte responses to parasite antigens

Key words

Trichinella spiralis Host resistance Immunotoxicity Immunosuppression Susceptibility to infection Parasite infections Methods 



Thanks to Mr. Carey Copeland and Ms. Debbie Andrews for excellent technical assistance in the development of the protocols, and to Drs. Christal Bowman and Marsha Ward for helpful comments and suggestions on the manuscript.


  1. 1.
    Luster MI, Portier C, Pait DG, Rosenthal GJ, Germolec DR, Corsini E, Blaylock BL, Pollock P, Kouchi Y, Craig W, White KL, Munson AE, Comment CE (1993) Risk assessment in immunotoxicology II. Relation­ships between immune and host resistance tests. Fundam Appl Toxicol 21:71–82CrossRefPubMedGoogle Scholar
  2. 2.
    Germolec DR (2004) Sensitivity and predictivity in immunotoxicity testing: immune endpoints and disease resistance. Toxicol Lett 149:109–114CrossRefPubMedGoogle Scholar
  3. 3.
    Luebke RW, Parks C, Luster MI (2004) Suppression of immune function and susceptibility to infections in humans: association of immune function with clinical disease. J Immunotoxicol 1:15–24CrossRefPubMedGoogle Scholar
  4. 4.
    Keil D, Luebke RW, Pruett SB (2001) Quantifying the relationship between multiple immunological parameters and host resistance: probing the limits of reductionism. J Immunol 167:4543–4552PubMedGoogle Scholar
  5. 5.
    Pozio E (1998) Trichinellosis in the European Union: Epidemiology, ecology and economic impact. Parasitol Today 14:35–38CrossRefPubMedGoogle Scholar
  6. 6.
    Roy SL, Lopez AS, Schantz PM (2003) Trichinellosis Surveillance – United States, 1997–2001. MMWR Surveill Summ 52(6):1–8PubMedGoogle Scholar
  7. 7.
    Vos JG, De Klerk A, Krajnc EI, van Loveren H, Rozing J (1990) Immunotoxicity of bis(tri-n-butyltin)oxide in the rat: effects on thymus-dependent immunity and on nonspecific resistance following long-term exposure in young versus aged rats. Toxicol Appl Pharmacol 105:144–155CrossRefPubMedGoogle Scholar
  8. 8.
    Luebke RW, Luster MI, Dean JH, Hayes HT (1984) Altered host resistance to Trichinella spiralis infection following subchronic exposure to diethylstilbestrol. Int J Immunopharmacol 6:609–617CrossRefPubMedGoogle Scholar
  9. 9.
    Luebke RW, Copeland CB, Deliberto JJ, Akubue PI, Andrews DL, Riddle MM, Williams WC, Birnbaum LS (1994) Assessment of host resistance to Trichinella spiralis in mice following preinfection exposure to 2, 3, 7, 8-TCDD. Toxicol Appl Pharmacol 125:7–16CrossRefPubMedGoogle Scholar
  10. 10.
    Luebke RW, Copeland CB, Andrews DL (1995) Host resistance to Trichinella spiralis infection in rats exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Fund Appl Toxicol 24:285–289CrossRefGoogle Scholar
  11. 11.
    Luebke RW, Copeland CB, Andrews DL (1999) Effects of aging on resistance to Trichinella spiralis infection in rodents exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Toxicology 136:15–26CrossRefPubMedGoogle Scholar
  12. 12.
    Goettsch W, Garssen J, Deijns A, de Gruijl FR, van Loveren H (1994) UV-B exposure impairs resistance to infection by Trichinella spiralis. Environ Health Perspect 102:298–301PubMedGoogle Scholar
  13. 13.
    Houben GF, Penninks AH, Seinen W, Vos JG, van Loveren H (1993) Immunotoxic effects of the color additive caramel color III: immune function studies in rats. Fundam Appl Toxicol 20:30–37CrossRefPubMedGoogle Scholar
  14. 14.
    Bell RG (1988) The generation and expression of immunity to Trichinella spiralis in laboratory rodents. Adv Parasitol 41:149–217CrossRefGoogle Scholar
  15. 15.
    Khan WI (2008) Physiological changes in the gastrointestinal tract and host protective immunity: learning from the mouse-Trichinella spiralis model. Parasitology 135:671–682CrossRefPubMedGoogle Scholar
  16. 16.
    Knight PA, Brown JK, Pemberton AD (2008) Innate immune response mechanisms in the intestinal epithelium: potential roles for mast cells and goblet cells in the expulsion of adult Trichinella spiralis. Parasitology 135:655–670CrossRefPubMedGoogle Scholar
  17. 17.
    Ruitenberg EJ, Elgersma A (1976) Absence of intestinal mast cell response in congenitally athymic mice during Trichinella spiralis infection. Nature 264:250–260CrossRefGoogle Scholar
  18. 18.
    Vos JG, Ruitenberg EJ, Van Basten N, Buys J, Elgersma A, Kruizinga W (1983) The athymic nude rat IV. Immunocytochemical study to detect T-cells, and immunological and histopathological reactions against Trichinella spiralis. Parasite Immunol 5:195–215CrossRefPubMedGoogle Scholar
  19. 19.
    Almond NM, Parkhouse RM (1986) Immunoglobulin class specific responses to biochemically defined antigens of Trichinella spiralis. Parasite Immunol 8:391–406CrossRefPubMedGoogle Scholar
  20. 20.
    Urban JF Jr, Schopf L, Morris SC, Orekhova T, Madden KB, Betts CJ, Gamble HR, Byrd C, Donaldson D, Else K, Finkelman FD (2000) Stat6 signaling promotes protective immunity against Trichinella spiralis through a mast cell- and T cell-dependent mechanism. J Immunol 164:2046–2052PubMedGoogle Scholar
  21. 21.
    McDermott JR, Bartram RE, Knight PA, Miller HRP, Garrod DC, Grencis RK (2003) Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc Nat Acad Sci USA 100:7761–7766CrossRefPubMedGoogle Scholar
  22. 22.
    Khan WI, Vallance BA, Blennerhassett PA, Deng Y, Verdu EF, Matthaei KI, Collins SM (2001) Critical role for signal transducer and activator of transcription factor 6 in mediating intestinal muscle hypercontractility and worm expulsion in Trichinella spiralis-infected mice. Infect Immun 69:838–844CrossRefPubMedGoogle Scholar
  23. 23.
    Vallance BA, Croitoru K, Collins SM (1998) T lymphocyte-dependent and independent intestinal smooth muscle dysfunction in the T. spiralis-infected mouse. Am J Physiol 275:G1157–G1165PubMedGoogle Scholar
  24. 24.
    Vallance BA, Galeazzi F, Collins SM, Snider DP (1999) CD4 T cells and major histocompatibility complex class II expression influence worm expulsion and increased intestinal muscle contraction during Trichinella spiralis infection. Infect Immun 67:6090–6097PubMedGoogle Scholar
  25. 25.
    Bell RG, Appleton JA, Negrao-Correa DA, Adams LS (1992) Rapid expulsion of Trichinella spiralis in adult rats mediated by monoclonal antibodies of distinct IgG isotypes. Immunology 75:520–527PubMedGoogle Scholar
  26. 26.
    Appleton JA, McGregor DD (1984) Rapid expulsion of Trichinella spiralis in suckling rats. Science 226:70–72CrossRefPubMedGoogle Scholar
  27. 27.
    Inaba T, Sato HA, Kamiya H (2003) Impeded establishment of the infective stage of Trichinella in the intestinal mucosa of mice by passive transfer of an IgA monoclonal antibody. J Vet Med Sci 65:1227–1231CrossRefPubMedGoogle Scholar
  28. 28.
    Ruitenberg EJ, Buys J, Teppema JS, Elgersma AZ (1983) Rat mononuclear cells and neutrophils are more effective than eosinophils in antibody-mediated stage-specific killing of Trichinella spiralis in vitro. Z Parasitenk 69:807–815CrossRefPubMedGoogle Scholar
  29. 29.
    Venturiello SM, Giambartolomei GH, Costantino SN (1993) Immune killing of newborn Trichinella larvae by human leucocytes. Parasite Immunol 15:559–564PubMedGoogle Scholar
  30. 30.
    Wang CH, Bell RG (1988) Antibody-mediated in-vivo cytotoxicity to Trichinella spiralis newborn larvae in immune rats. Parasite Immunol 10:293–308CrossRefPubMedGoogle Scholar
  31. 31.
    Lee TD, Befus D (1989) Effects of rat and human intestinal lamina propria cells on viability and muscle establishment of Trichinella spiralis newborn larvae. J Parasitol 75:124–128CrossRefPubMedGoogle Scholar
  32. 32.
    Gurish MF, Bryce PJ, Tao H, Kisselgof AB, Thornton EM, Miller HR, Friend DS, Oettgen HC (2004) IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis. J Immunol 172:1139–1145PubMedGoogle Scholar
  33. 33.
    Dessein AJ, Parker WL, James SL, David JR (1981) IgE antibody and resistance to infection I. Selective suppression of the IgE antibody response in rats diminishes the resistance and the eosinophil response to Trichinella spiralis infection. J Exp Med 153:423–436CrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Immunotoxicology Branch, Division of National Health and Environmental EffectsUnited State Environmental Protection AgencyDurhamUSA

Personalised recommendations