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Schistosoma mansoni: Influence of immunization and challenge schedules on the sites and mechanisms of resistance in CBA/Ca mice vaccinated with highly irradiated cercariae

Published online by Cambridge University Press:  05 June 2009

A. A. F. Elsaghier
Affiliation:
Divsion of Parasitology, National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK
Diane J. McLaren
Affiliation:
Divsion of Parasitology, National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

Abstract

These studies address current controversies over the site(s) of challenge attrition in the murine irradiated vaccine model of immunity to Schistosoma mansoni. Two possibilities have been investigated. Firstly, that the site of death of the radiation-attenuated schistosomes used to vaccinate the mice may vary in different laboratories and secondly, that the skin sites selected for presentation of the immunizing and challenge parasites may influence the final site at which immunity is effected (i.e. ear/abdomen vs tail/tail). The migration of radiolabelled cercariae exposed to 0, 20 or 50 krad of gamma irradiation from the NIMR 60Cobalt source was examined in CBA/Ca mice by squashed organ autoradiography. Unirradiated parasites all migrated from the skin to the lungs, and 65% moved on to the liver. Migration of parasites attenuated by exposure to 20 krad of gamma irradiation was delayed, but 76% finally reached the lungs; only 1% was recruited to the liver. The majority of 50 krad attenuated parasites died in the skin, with only 4% accomplishing migration to the pulmonary vasculature. The major site of death (and by implication of antigenic stimulation) of the 20 krad attenuated NIMR strain S. mansoni used routinely for vaccination purposes in our laboratory, is thus the lungs, a finding that does not explain the fact that immunity is mediated primarily in the skin in our model system. Site elimination experiments and squashed organ autoradiography showed conclusively that, irrespective of the skin sites chosen for presentation of the immunizing and challenge population of worms, NIMR challenge parasites are killed predominantly in the skin of vaccinated CBA/Ca mice. Moreover, qualitative and quantitative histological examination of the challenged tail skin of vaccinated mice revealed that inflammatory reactions comprising mononuclear cells and eosinophils develop in this site and function to trap and eliminate challenge larvae, despite a reported reduction in antigen presenting cells in this region.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1989

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References

REFERENCES

Bergstresser, P. R., Fletcher, C. R. & Streilein, J. W. (1980a) Surface densities of Langerhans' cells in relation to rodent epidermal sites with special immunologic properties. Journal of Investigative Dermatology, 74, 7780.CrossRefGoogle ScholarPubMed
Bergstresser, P. R., Tows, G. B., Gilliam, J. N. & Streilein, J. W. (1980b) Unusual numbers and distributions of Langerhans cells in the skin with unique immunologic properties. Journal of Investigative Dermatology, 74, 312314.CrossRefGoogle ScholarPubMed
Bickle, Q. D. (1982) Studies on the relationship between the survival of Schistosoma mansoni larvae in mice and the degree of resistance produced. Parasitology, 84, 111122.CrossRefGoogle ScholarPubMed
Christensen, N. O. (1977) A method for the in vitro labelling of Schistosoma mansoni and Schistosoma intercalatum cercariae with radioselenium. Zeitschrift für Parasitenkunde, 54, 275288.CrossRefGoogle Scholar
Dean, D. A., Mangold, B. L., Georgi, J. R. & Jacobson, R. H. (1984) Comparison of Schistosoma mansoni migration patterns in normal and irradiated cercaria-immunized mice by means of autoradiographic analysis. Evidence that worm elimination occurs after the skin phase in immunized mice. American Journal of Tropical Medicine and Hygiene, 33, 8996.CrossRefGoogle ScholarPubMed
James, S. L. (1987) Induction of protective immunity against Schistosoma mansoni by a non-living vaccine is dependent on the method of antigen presentation. Journal of Immunology, 134, 19561960.CrossRefGoogle Scholar
James, E. R. & Dobinson, A. R. (1983) Comparison of the protective resistance induced by 60Co-irradiated cercariae and schistosomula of the WFFS and NMRI strains of Schistosoma mansoni. Journal of Helminthology, 59, 313317.CrossRefGoogle Scholar
Kamiya, H. & Mclaren, D. J. (1987) Schistosoma mansoni: migration potential of normal and radiation attenuated parasites in naive guinea pigs. Experimental Parasitology, 63, 98107.CrossRefGoogle ScholarPubMed
Kamiya, H., Smithers, S. R. & Mclaren, D. J. (1987) Schistosoma mansoni: autoradiographic tracking studies of isotopically labelled challenge parasites in naive and vaccinated CBA/Ca mice. Parasite Immunology, 9, 515529.CrossRefGoogle ScholarPubMed
Mangold, B. L. & Dean, D. A. (1983) Autoradiographic analysis of Schistosoma mansoni migration from skin to lungs in naive mice. Evidence that most attrition occurs after the skin phase. American Journal of Tropical Medicine and Hygiene, 32, 785789.CrossRefGoogle ScholarPubMed
Mangold, B. L. & Dean, D. A. (1984) The migration and survival of gamma-irradiated Schistosoma mansoni larvae and the duration of host-parasite contact in relation to the induction of resistance in mice. Parasitology, 88, 249266.CrossRefGoogle Scholar
Mangold, B. L., Dean, D. A., Coulson, P. S. & Wilson, R. A. (1986) Site requirements and kinetics of immune-dependent elimination of intravascularly administered lung stage schistosomula in mice immunized with highly irradiated cercariae of Schistosoma mansoni. American Journal of Tropical Medicine and Hygiene, 35, 332344.CrossRefGoogle ScholarPubMed
Mastin, A. J., Bickle, Q. D. & Wilson, R. A. (1983) Schistosoma mansoni: migration and attrition of irradiated and challenge schistosomula in the mouse. Parasitology, 87, 87102.CrossRefGoogle ScholarPubMed
McLaren, D. J., Pearce, E. J. & Smithers, S. R. (1985) Site potential for challenge attrition in mice, rats and guinea pigs vaccinated with irradiated cercariae of Schistosoma mansoni. Parasite Immunology, 7, 2944.CrossRefGoogle ScholarPubMed
McLaren, D. J. & Smithers, S. R. (1987) The immune response to schistosomes in experimental hosts. In: The Biology of Schistosomes (editors, Rollinson, D. & Simpson, A. J. G.) pp. 233263. Academic Press: London.Google Scholar
McLaren, D. J. & Smithers, S. R. (1988) Serum from CBA/Ca mice vaccinated with irradiated cercariae of Schistosoma mansoni protects naive recipients through the recruitment of cutaneous effector cells. Parasitology, 97, 287302.Google ScholarPubMed
McLaren, D. J., Strath, M. & Smithers, S. R. (1987) Schistosoma mansoni: evidence that immunity in vaccinated and chronically infected mice involves cutaneous effector mechanisms that are sensitive to treatment with anti-leucocyte monoclonal antibodies. Parasite Immunology, 9, 667–282.CrossRefGoogle Scholar
Miller, K. L. & Smithers, S. R. (1982) Localized skin changes at the site of immunization with highly irradiated cercariae of Schistosoma mansoni are associated with enhanced resistance to a challenge infection. Parasitology, 85, 305314.CrossRefGoogle ScholarPubMed
Miller, K. L., Smithers, S. R. & Sher, A. (1981) The response of mice immune to Schistosoma mansoni to a challenge infection which bypasses the skin: evidence for two mechanisms of immunity. Parasite Immunology, 3, 2531.CrossRefGoogle ScholarPubMed
Smithers, S. R. & Gammage, K. (1980) Recovery of Schistosoma mansoni from the skin, lungs and hepatic portal system of naive mice and mice previously exposed to S. mansoni: evidence for two phases of parasite attrition in immune mice. Parasitology, 80, 289300.CrossRefGoogle Scholar
Smithers, S. R. & Terry, R. J. (1965) The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adult worms. Parasitology, 55, 695700.CrossRefGoogle ScholarPubMed
Ward, R. M. & McLaren, D. J. (1988) Schistosoma mansoni: evidence that eosinophils and/or macrophages contribute to skin-phase challenge attrition in vaccinated CBA/Ca mice. Parasitology, 96, 6384.CrossRefGoogle ScholarPubMed
Wilson, R. A., Coulson, P. S. & Dixon, B. (1986) Migration of Schistosoma mansoni in mice vaccinated with radiation-attenuated cercariae, and normal mice: an attempt to identify the timing and site of parasite death. Parasitology, 92, 101116.CrossRefGoogle ScholarPubMed