Transcriptional responses of mouse proximal colon and colonoids during early whipworm infection

The human whipworm causes trichuriasis and infects 289 million people, but the molecular mechanisms of early infection are poorly understood, limiting effective control development. We examined host transcriptional responses during early infection with the mouse whipworm Trichuris muris, using in vivo and in vitro models: C57BL/6 (B6) mice, STAT6-deficient (STAT6KO) mice, and proximal colon organoids (colonoids). Extensive differential gene expression and alternative splicing (AS) events were observed, including downregulation of 'lipid metabolism' pathways in both mice models (also modulated in colonoids), upregulation of the 'neurotransmitter release' pathway in B6, suggesting a role in modulating intestinal inflammation, and enrichment of alternative splicing-related pathways among AS genes. Temporal transcriptomic profiling of T. muris first-stage larvae (L1) in colonoids identified six gene clusters representing distinct functional pathways. These results provide insights into transcriptional rewiring during early whipworm infection in different infection models and underscore the application of colonoids in understanding early whipworm infection.