Campylobacter jejuni Infection Is Associated With Cell-Cycle, Redox, and Metabolic Remodeling of Human Intestinal Epithelial Cells at Single-Cell Resolution

Campylobacter jejuni, a major cause of bacterial enteric infections, is linked to significant disruptions in human intestinal epithelial cells at a single-cell level. A study, conducted using single-cell RNA sequencing on Caco-2 cells, has identified key transcriptional states and the cells' response to C. jejuni infection. The research revealed a redistribution of cellular clusters and increased representation of G2/M-classified cells, alongside coordinated activation of checkpoint and mitotic-spindle genes such as CDKN1A, WEE1, MAD2L1, BUB1B, PLK1, CDC20, CDK1, and UBE2C.

The study also identified a Reactome mitotic spindle checkpoint program, enriched by C. jejuni infection, with a normalized enrichment score of ~1.67 and false discovery rate of ~0.013. Additionally, Hallmark analysis indicated strong activation of TNF/NF-kB, hypoxia, G2M checkpoint, TGF-beta, glycolysis, apoptosis, p53, and mTORC1-associated programs. Furthermore, infection led to a noticeable decrease in JDP2 expression and an increase in NOX1 and DUOX2 gene expression.

This investigation highlights the profound and coordinated impact of C. jejuni infection on host transcriptional responses, providing valuable insights into the heterogeneity and cellular mechanisms involved in intestinal inflammation and damage.