Single-cell transcriptomics of Encephalitozoon intestinalis infection in Caco-2 and Vero cells

Microsporidia are single-celled, obligate intracellular parasites closely related to fungi. One of the most common human-infecting microsporidian species, Encephalitozoon intestinalis , is an enteric parasite that invades and replicates within the epithelial lining of the small intestine. Two epithelial cell lines, Caco-2 and Vero cells, are routinely used as in vitro models of E. intestinalis infection. Here, we use scRNA-seq to investigate the host response to E. intestinalis infection and the transcriptional dynamics of parasite development in both Caco-2 and Vero cell lines. We observe that most host cells have no direct transcriptional response to parasite invasion or intracellular replication, suggesting that cells fail to detect and/or fail to respond to direct E. intestinalis infection, consistent with previous single-cell transcriptomics of E. intestinalis -infected macrophages. Our data suggest that a small subset of host cells detect intracellular parasites late in the life cycle, and signal to neighboring cells, leading to broad activation of a TNF-α response. Analysis of parasite transcripts reveals a developmental program that correlates with the morphological stages of the parasite life cycle. Together our data provide insights into a shared host transcriptional response to E. intestinalis infection and the datasets presented are a valuable resource for future studies.