Functional genomics of intramolluscan stages of the human blood fluke, Schistosoma mansoni: Role of antioxidants in parasite defense

The ability of the larval forms of the digenetic trematode, Schistosoma mansoni, to invade and parasitize their molluscan host, Biomphalaria glabrata is determined by a multitude of factors related to the host-parasite relationship. However, very little is known regarding the specific genes regulating schistosome growth and reproduction within the snail host, and represents a critically important gap in our knowledge of schistosome biology. Therefore, the purpose of this work was to identify genes involved either directly or indirectly in the transformation and development of the early intramolluscan larval stages. Gene expression profiling of the free-swimming miracidial and parasitic sporocyst stages of S. mansoni using DNA microarrays and Serial Analysis of Gene Expression (SAGE) has led to speculation into possible mechanisms by which the invading larvae are able to counteract the snail immune response, specifically, the encapsulation of sporocysts by circulating hemocytes followed by production of reactive oxygen species (ROS) through the action of a respiratory burst. The production of ROS, in particular hydrogen peroxide (H2O2) and nitric oxide (NO), results in the rapid death of schistosome larvae. As a protective mechanism, it has been proposed that S. mansoni sporocysts produce antioxidant molecules in order to counteract host ROS as well as oxidative products produced through their own metabolism. Subsequent experiments determined the expression levels of parasite antioxidant genes during early larval development, the immunolocalization of two upregulated peroxiredoxin (Prx) proteins on the surface of developing sporocysts and in the excretory/secretory products of transforming larvae, and showed the specific H2O2 detoxifying activity of those Prx proteins in vitro. These studies suggest that S. mansoni larvae possess a functional, thiol-dependent antioxidant system that appears to constitute a frontline of defense against host ROS, therefore, permitting the establishment of a successful infection within the snail intermediate host. Further study of parasite anti-immune responses may lead to methods of blocking transmission of this important human pathogen.