Research Article: Temporal modulation of gene expression in a controlled Schistosoma mansoni human infection model
Abstract:
Schistosomiasis is caused by parasitic blood flukes of the genus Schistosoma . Despite ongoing mass drug administration efforts, the disease remains a major public health burden in endemic regions. A better understanding of early host responses to schistosomiasis is critical for developing effective vaccines and therapeutics.
We conducted a longitudinal transcriptomic study of peripheral blood samples from 30 Schistosoma -naïve volunteers participating in two controlled human infection trials with male- or female-only S. mansoni cercariae. Blood was collected at six time points over 20 weeks post-infection. Whole-transcriptome RNA sequencing and integrative analyses, including differential gene expression, gene set enrichment, protein interaction networks, co-expression clustering, and immune module profiling, were employed to characterize temporal modulation of genes related to immune responses.
Robust and highly time-dependent transcriptional responses were observed, peaking at Week 4 post-infection. Differential gene expression and pathway analyses revealed activation of immune responses, including type I and II interferon signaling, chemokine-mediated pathways, and antigen presentation. Notably, both Th1 and Th2 signatures were evident at Week 4. Key immune hubs included IFNG , TNF , and IL1B , along with transcriptional regulators such as STAT1 and IRF7 . Blood transcription module analysis further highlighted transient activation of interferon and plasma cell-related responses.
This study provides a comprehensive transcriptional map of early host responses to S. mansoni infection in humans. The findings underscore the central role of interferon pathways, early mixed Th1/Th2 polarization, and inflammation-associated gene signatures in shaping host response to S. mansoni infection. These insights may inform the rational design of vaccines and biomarkers for schistosomiasis.
Introduction:
Schistosomiasis is caused by parasitic blood flukes of the genus Schistosoma . Despite ongoing mass drug administration efforts, the disease remains a major public health burden in endemic regions. A better understanding of early host responses to schistosomiasis is critical for developing effective vaccines and therapeutics.
Read more