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

Abstract

ABSTRACTThese studies address current controversies over the site(s) of challenge attrition in the murine irradiated vaccine model of immunity toSchistosoma 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 NIMR60Cobalt 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 strainS. mansoniused 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.