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Publication : Analysis of intestinal epithelial cell responses to Cryptosporidium highlights the temporal effects of IFN-γ on parasite restriction.

First Author  Pardy RD Year  2024
Journal  PLoS Pathog Volume  20
Issue  5 Pages  e1011820
PubMed ID  38718306 Mgi Jnum  J:348251
Mgi Id  MGI:7639114 Doi  10.1371/journal.ppat.1011820
Citation  Pardy RD, et al. (2024) Analysis of intestinal epithelial cell responses to Cryptosporidium highlights the temporal effects of IFN-gamma on parasite restriction. PLoS Pathog 20(5):e1011820
abstractText  The production of IFN-gamma is crucial for control of multiple enteric infections, but its impact on intestinal epithelial cells (IEC) is not well understood. Cryptosporidium parasites exclusively infect epithelial cells and the ability of interferons to activate the transcription factor STAT1 in IEC is required for parasite clearance. Here, the use of single cell RNA sequencing to profile IEC during infection revealed an increased proportion of mid-villus enterocytes during infection and induction of IFN-gamma-dependent gene signatures that was comparable between uninfected and infected cells. These analyses were complemented by in vivo studies, which demonstrated that IEC expression of the IFN-gamma receptor was required for parasite control. Unexpectedly, treatment of Ifng-/- mice with IFN-gamma showed the IEC response to this cytokine correlates with a delayed reduction in parasite burden but did not affect parasite development. These data sets provide insight into the impact of IFN-gamma on IEC and suggest a model in which IFN-gamma signalling to uninfected enterocytes is important for control of Cryptosporidium.
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