Authors
F Winkelmann1; C Schulz1; D Koczan1; E C Reisinger1; M Sombetzki1; 1 University Medical Center Rostock, Germany Discussion
Intestinal Schistosomiasis, caused by the helminth parasite Schistosoma mansoni, results in hepatosplenic disease triggered by parasite eggs trapped in the liver. Beside the egg antigens, antigens of gonochoric adult worms circulate in the blood of the host. We have recently reported that unisexual infection differentially affects the host immune system. However, there are limited data on the sex-specific immunogenic potential. To dissect the underlying mechanisms of differential immunogenicity of female and male worms, we performed comparative transcriptomic and flow cytometric analyses of spleen tissue from unisexually and bisexually infected mice and examined the immunostimulatory capacity of splenocytes. We identified a total of 1293, 512 or 4062 genes, respectively, that were differentially expressed in group male-only (M), female-only (F), or male and female (MF) infected mice compared to naive controls. Both, bisexual infection and unisexual infection with male worms strongly effects the host’s immune response, erythrocyte homeostasis, lipoprotein metabolism and cell cycle processes. In contrast, unisexual infection with females shows little effects on the host immune system. Flow cytometric analysis of splenocytes revealed that recruitment of granulocytes to the spleen is induced by the eggs rather than by the worm itself. Furthermore, the data suggest that in the absence of eggs, the male worm affects the maturation of dendritic cells by upregulating CD86. Isolated splenocytes of all experimental groups secreted Th2- cytokines IL-4 and IL-13 upon stimulation with soluble worm/egg antigen. However, exclusively the splenocytes from mice infected with male worm secreted IL-10 upon stimulation. Our study sheds more light on the previously described differences between the immunomodulatory properties of male and female worms and contributes to a better understanding of the immunological interaction between host and adult schistosomes and can be used in the future to identify new targets for innovative therapies against schistosomiasis. 
