Elucidation of the mechanism of action of antischistosomal compound SAS1 by host immune cell functional analysis

The neglected tropical disease schistosomiasis impacts over 240 million individuals across the world, leads to viral organ damage, and causes among the highest incidences of parasite-related mortality worldwide. Praziquantel (PZ) is the currently available treatment but has efficacy only against the adult worm. The newly discovered antischistosomal compound SAS1 has previously proven to have a higher efficacy against both juvenile and mature parasites in mice and monkeys compared to PZ in vivo. However, SAS1 kills the parasite outside of its host only at extremely high concentrations, indicative of a host-dependent mechanism of action. The purpose of this study is to investigate a possible mechanism of SAS1 as a compound which facilitates the activation of the host immune system. It is hypothesized that murine eosinophils treated with SAS1 will be primed to undergo increased levels of chemotaxis and degranulation, measurable by immunohistochemistry and a release in the granulocytic proteins eosinophil peroxidase and superoxide anions respectively. Male mice were either orally administered SAS1 or vehicle control, and sixteen hours post-treatment, eosinophils were isolated from mouse spleens by magnetic separation. Eosinophil peroxidase levels were determined by enzyme-linked immunosorbent assay, and superoxide anion concentrations were measured by calculating the reduction of cytochrome c. Preliminary results show that the experimental drug increased innate immune cell degranulation following stimulation. This work and future studies on SAS1 may progress the release of this treatment for schistosomiasis in order to combat resistance to PZ and introduce treatment early in infection