Utilisation of "Omics" to unmask the interactions of adult male and female Schistosoma mansoni with their host

Abstract text

Introduction: Schistosoma spp. are gonochoristic trematodes that cause one of the most devastating worm parasitoses in the world. To date, there is no effective vaccine to protect against the infection, and drug treatment with praziquantel has limited success in endemic areas. In the search for new therapeutic approaches to combat this disease, adult female schistosomes have so far been neglected because they have little direct contact with the environment and thus with the host during their mating with male worms.

Objectives: Using "Omic" technologies, we aim to study the interactions between adult male and female Schistosoma mansoni and their host to find targets for new therapeutic strategies.

Materials & methods: First, we studied the structure of the tegument of male and female unpaired and paired schistosomes after contact with human serum as the host interface. Comparative analyses were performed by electron microscopy and immunohistochemistry. In addition, the tegument proteome of male and female unpaired and paired schistosomes was examined using a novel and highly sensitive workflow by LC-MS/MS analysis. In addition, the effect of circulating antigens from male and female schistosomes on the host immune response was investigated. For this purpose, the transcriptome and immune cell populations in the spleens of unisexually infected mice were analyzed.

Results: After incubation in human serum, adult male and female schistosomes exhibited marked surface enlargement, and females showed shedding of their outer surface. Using proteomic analyses, we identified 1519 tegument proteins for male and female unpaired and paired schistosomes. We identified more proteins in male than in female worms, regardless of whether they were derived from mating or from unisexual infection. For transcriptomic analyses, 22,207 transcripts were examined in the spleens of unisexually infected mice. Principal component analysis showed clear clustering of experimental groups. Our studies suggest that male and female S. mansoni elicit an egg-independent, non-polarized Th1/Th2 immune response in the host, with males having a significantly greater immunoregulatory influence on gene regulation in the spleen and thus on the host.

Conclusion: Our initial prelimiary findings need to be investigated to discover and understand new metabolic pathways and immunomodulatory mechanisms of adult worms to contribute to the development of new therapeutic strategies against schistosomiasis.