EPICURE: assessing the epigenetic changes in Schistosoma mansoni developmental trajectory after in vitro treatment with serum from schistosomiasis self-cured rhesus macaques

Abstract

Schistosomiasis affects millions of people, being considered a global public health problem. It is caused by schistosomes, flatworm flukes widely distributed around the world. Non-human vertebrate hosts of schistosomes are usually good models to understand the dynamics of schistosomiasis. At least 21 species of mammals have been found infected with this parasite in Africa and America. Among them, rhesus macaques are unusual schistosome hosts presenting a self-cure from an established infection and thereafter manifesting solid immunity against a challenge. It is known from the literature that prefusion of rhesus macaques infected with S. mansoni, 18 weeks after infection, recovers worms that are shrunken and pallid, with degenerative changes in intestines and reproductive organs, indicating that the development and maturation from schistosomula to adult worms was impaired. However, very little is known about how rhesus macaques are able to self-cure from the Schistosoma infection and about the effect of infected rhesus serum on S. mansoni parasites development and growth. In this context, it is known that blood-feeding S. mansoni schistosomula which were cultured in vitro with serum from self-cured rhesus macaques showed a significant reduction (approximately 50%) of schistosomula growth. On the other hand, it is known that modifications and reprograming of chromatin structure are essential for Schistosoma development. However, the epigenetic changes in chromatin (and ultimately on gene expression programs) caused by the serum from self-cured rhesus macaques related to this reduction in schistosomula growth are totally unknown. Our proposal is to evaluate the epigenetic changes on chromatin structure from schistosomula that can be responsible for the reduction on schistosomula growth after treatment with self-cured rhesus macaques' serum. Specifically, we will add rhesus serum to schistosomula in vitro cultures and perform ChIP (chromatin immunoprecipitation) followed by qPCR (quantitative real time PCR) to evaluate the changes on histone 3 trimethylated lysine 4 (H3K4me3), acetylated lysine 9 (H3K9ac), trimethylated lysine 9 (H3K9me3) and trimethylated lysine 27 (H3K27me3) that may have occurred on the genomic regions of a set of selected genes involved on schistosomula growth and metabolism. These analyses will help to understand the molecular basis of the effect of self-cured rhesus' serum on the chromatin structure of schistosomula and on target genes. This information may provide suitable Schistosoma molecular targets, and possible new therapeutic and vaccine candidates against schistosomiasis. (AU)