Conference Agenda

Schistosomiasis-induced fibrosis, driven by host immune response to trapped eggs, is the principal cause of pathology and schistosomiasis-related morbidity. While praziquantel effectively clears adult parasites, no therapies exist to target egg or egg-induced tissue fibrosis. To address gaps in fibrosis-related cellular mechanisms and identify novel antifibrotic targets, we used single-cell spatial transcriptomics with a 5000-gene mouse panel to map the molecular architecture of hepatic and intestinal fibrotic regions in Schistosoma mansoni-infected mice. Results showed that schistosome-induced granulomas are highly organized and overlap with fibrotic regions in both tissues at 8 weeks post-infection. Differential expression analysis identified 1175 genes in 534k liver cells and 807 genes in 259k intestine cells significantly altered between healthy control and infected samples. These DEGs are strongly associated with cytokine and interleukin signaling, TGF‑β pathway, and extracellular matrix organization. The cell types enriched in infected regions included macrophages, collagen-producing cells (liver-activated hepatic stellate cells, intestine-activated fibroblasts), eosinophil-like cells, T, B, and plasma cells. Furthermore, cell-cell interaction analysis revealed strong interactions between macrophages and collagen-producing cells in infected tissues. While many identified ligand-receptor pairs are organ-specific, a core signature of 5 pairs (including Col1a2/Tgm2-Itgb1) was shared across tissues, representing potential pan-tissue therapeutic targets for schistosome-induced fibrosis.