Characterization of Transcriptional, Epigenetic, and Phenotypic Plasticity and Discovery of Biomarkers in Acute and Chronic Murine Schistosomiasis Infection

Parasites can induce changes in their hosts, favoring the success of the infection and its development at each stage of their life cycle. The host minimizes the effects of the parasite's presence through its defense system, balancing the parasite-host relationship. The intricate parasite-host relationship provides physiological, immunological, and molecular cues that suggest interaction and mutual regulation of the transcriptome and epigenome, promoting phenotypic plasticity and survival in a changing environment. There has been a growing interest in the epigenetic mechanisms of Schistosoma mansoni, a parasite with remarkable phenotypic plasticity in response to signals from the environment and its hosts. Several studies emphasize the epigenetic mechanisms behind the phenotypic plasticity of Schistosoma. Regarding the host's gene expression in the face of infection, however, there is little evidence of which pathways are altered by the passage of the parasite through the lungs and by the pathogenesis in the hepatic portal system. In this work, we characterized S. mansoni infection in parasitological and biochemical aspects of the murine model in comparison with the profile of the initial, acute, and chronic phases of infection (3, 7, and 20 wpi (weeks postinfection), respectively). The biochemical and morphological results of the infection at 3, 7, and 20 wpi show the phenotypic changes of schistosomiasis in the murine model. ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) at 7 wpi shows a chromatin with higher accessibility for infected individuals, and Western blotting at 7 wpi shows an increase in histone marks H3K9ac and H3K9me3, indicating a change in chromatin status after infection. RNA-seq (RNA sequencing) for 7 wpi results show a differential profile of lipid metabolism genes that are negatively modulated, while immune system genes are positively modulated. It is interesting to note that the negative modulation of mRNA expression of lipid pathway genes causes the rates of these metabolites to appear decreased in the blood, while the increased expression of immune system defense genes is in accordance with liver histology data, which shows an inflammatory profile.