Amphotericin B-induced resistance to Schistosoma mansoni

Amphotericin B (AmB) increases host resistance against several infectious agents and tumors. We evaluated its effect on infections with the helminth Schistosoma mansoni. A single dose of 500 μg i.p. or 25 μg i.v. increased resistance in mice to a challenge with 500 or 100 S. mansoni cercariae. Schistosomula recovery from the lungs, 5 days after challenge, was reduced 33 to 40%. Adult worm recovery 8 wk after injection was reduced 36 to 43%, AmB was effective in protecting mice when given from 9 days before until the day of cercarial challenge but was ineffective 2 wk before or at all intervals after S. mansoni infection. To examine the mechanism of this resistance, we obtained peritoneal exudate cells (PEC) from animals treated with AmB and assessed their ability to kill schistosomula, the migrating larval stage of the parasite. Killing by adherent PEC 1 or 2 days after AmB treatment was the same as that of resident macrophages from untreated animals. Adherent PEC from animals 3 to 7 days after AmB treatment showed enhanced killing of schistosomula (38.0 ± 3.0% at day 4, which exceeded control of 8.1 ± 4.0, p <0.01). These PEC also displayed increased killing of Staphylococcus aureus. When AmB was added to cultures of resident peritoneal adherent cells from untreated mice at 0.5 μ/ml to 2.0 μg/ml (concentrations not toxic to the organism), schistosomula killing was increased 1- to 6-fold. These findings demonstrate activation of murine macrophages by AmB in vitro and in vivo, which results in greater killing of this multicellular parasite and potentially contributes to enhanced resistance to infection.