Parasite Challenge as Host Resistance Models for Immunotoxicity Testing
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 wordsTrichinella 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.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
- 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
- 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