Schistosoma mansoni soluble egg antigens trigger erythrocyte cell death.

Estimated to affect nearly 300 million people worldwide, schistosomiasis is caused by parasitic flatworms of the genus Schistosoma. The major pathological consequences of chronic schistosomiasis are associated with soluble egg antigens (SEA) secreted from schistosome egg deposits in liver and other organs. The vigorous immune responses induced by egg antigens result in granuloma formation and other pathophysiological symptoms such as hepatosplenomegaly and anemia. Risk of anemia correlates with infection intensity and the level of host hemoglobin is inversely proportional to egg count. Schistosomiasis-associated anemia could be multifactorial, but the potential link and molecular underpinnings are unclear. Here, we evaluate whether S. mansoni SEA affects survival of mouse erythrocytes. Erythrocytes incubated with different concentrations of SEA were tested for various markers of erythrocyte cell death. Erythrocytes exposed to SEA exhibit elevated intracellular Ca(2+) levels as measured by Fluo-3 AM fluorescence in flow cytometry, and they also display concentration-dependent, Ca(2+)-dependent, and heat-sensitive increases in phosphatidyl serine exposure. Further, SEA-exposed erythrocytes show increased fluorescence using the in situ apoptosis marker CaspACE FITC, indicating the involvement of caspase-mediated cell deformation. Taken together, these results offer several lines of experimental evidence for SEA-induced erythrocyte cell death and may provide new insights into factors contributing to schistosomiasis-associated anemia.