Analysis of intestinal epithelial cell responses to Cryptosporidium highlights the temporal effects of IFN-γ on parasite restriction.
Ryan D PardyKatelyn A WalzerBethan A WallbankJessica H ByerlyKeenan M O'DeaIan S CohnBreanne E HaskinsJustin L RoncaioliEleanor J SmithGracyn Y BuenconsejoBoris StriepenChristopher A HunterPublished in: PLoS pathogens (2024)
The production of IFN-γ 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-γ-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-γ receptor was required for parasite control. Unexpectedly, treatment of Ifng-/- mice with IFN-γ 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-γ on IEC and suggest a model in which IFN-γ signalling to uninfected enterocytes is important for control of Cryptosporidium.
Keyphrases
- dendritic cells
- plasmodium falciparum
- immune response
- single cell
- toxoplasma gondii
- trypanosoma cruzi
- transcription factor
- hiv infected
- rna seq
- life cycle
- genome wide
- high throughput
- cell death
- risk factors
- dna methylation
- adipose tissue
- machine learning
- gene expression
- electronic health record
- big data
- antiretroviral therapy
- dna binding
- combination therapy
- deep learning
- signaling pathway
- high fat diet induced
- long non coding rna