Spatial transcriptomics reveals focal induction of molecular responses and cellular interactions in the small intestine during Heligmosomoides polygyrus Infection

The infective L3 larvae of Heligmosomoides polygyrus migrate to the small intestine where they take up residence in the submucosa, triggering the formation of complex granulomas around the parasite. Here, we employ spatial transcriptomics to elucidate the transcriptional intricacies and cell-cell interactions of the murine small intestine under both steady-state conditions and in response to H. polygyrus infection. Our findings unveil distinct transcriptional signatures in the crypt zone, villi, and granulomas, providing nuanced insights into the molecular dynamics of the host response to parasitic infection. Molecular characterization of H. polygyrus granulomas reveals unique cellular compositions within distinct clusters, shedding light on localized immune activation and cellular dynamics. Utilizing deconvolution techniques, we uncovered common and infection-specific signatures of cell type colocalization, and identified potential ligand-receptor pairs that may mediate communication between the granuloma tissue and the epithelial crypt cells. Additionally, our study highlights the upregulation of genes such as Ccl9, Fcer1g and Tmsb4x within granulomas, suggesting roles in type 2 inflammation, and genes (e.g Reg3b and Mxra7 ) associated with wound healing and tissue repair. These results not only enhance our understanding of the murine small intestine’s transcriptional landscape but also provide a platform for exploring host-pathogen interactions. The comprehensive analysis presented here contributes to a holistic comprehension of tissue-specific responses during parasitic infections, offering valuable insights for targeted therapeutic interventions.